US 2016O1861 68A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka et al. (43) Pub. Date: Jun. 30, 2016

(54) PROCESSES AND HOST CELLS FOR Related U.S. Application Data GENOME, PATHWAY. AND BIOMOLECULAR (60) Provisional application No. 61/938,933, filed on Feb. ENGINEERING 12, 2014, provisional application No. 61/935,265, - - - filed on Feb. 3, 2014, provisional application No. (71) Applicant: ENEVOLV, INC., Cambridge, MA (US) 61/883,131, filed on Sep. 26, 2013, provisional appli (72) Inventors: Jay H. Konieczka, Cambridge, MA cation No. 61/861,805, filed on Aug. 2, 2013. (US); James E. Spoonamore, Publication Classification Cambridge, MA (US); Ilan N. Wapinski, Cambridge, MA (US); (51) Int. Cl. Farren J. Isaacs, Cambridge, MA (US); CI2N 5/10 (2006.01) Gregory B. Foley, Cambridge, MA (US) CI2N 15/70 (2006.01) CI2N 5/8 (2006.01) (21) Appl. No.: 14/909, 184 (52) U.S. Cl. 1-1. CPC ...... CI2N 15/1082 (2013.01); C12N 15/81 (22) PCT Filed: Aug. 4, 2014 (2013.01); C12N 15/70 (2013.01) (86). PCT No.: PCT/US1.4/49649 (57) ABSTRACT S371 (c)(1), The present disclosure provides compositions and methods (2) Date: Feb. 1, 2016 for genomic engineering. Patent Application Publication Jun. 30, 2016 Sheet 1 of 4 US 2016/O186168 A1

Patent Application Publication Jun. 30, 2016 Sheet 2 of 4 US 2016/O186168 A1

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Patent Application Publication Jun. 30, 2016 Sheet 4 of 4 US 2016/O186168 A1

US 2016/01 86168 A1 Jun. 30, 2016

PROCESSES AND HOST CELLS FOR 0006. In various aspects, the invention is applicable to GENOME, PATHWAY. AND BIOMOLECULAR phenotype engineering, including but not limited to: change ENGINEERING in carbon Substrate utilization, increased cell growth rate, increased production of a desired chemical, redox cofactor PRIORITY balance, reduced production of one or more undesired 0001. This application claims benefit of and priority to byproducts, increased resistance to industrial fermentation, U.S. Provisional Application No. 61/861,805 filed Aug. 2, and increased recombinant protein production, among others. 2013,61/883,131 filed Sep. 26, 2013, 61/935,265 filed Feb.3, In some embodiments, the phenotype relates to pathway engi 2014, and 61/938,933 filed Feb. 12, 2014, each of which is neering, such as where metabolic flux through a core or hereby incorporated by reference in its entirety. primary metabolic pathway is significantly altered (e.g., Sig nificantly altered as compared to wild type strain, an unengi FIELD OF THE INVENTION neered strain, or a starting strain), including alteration of metabolic flux through one or more intermediates that repre 0002. The invention relates to, inter alia, methods and sent metabolic branch points. In various embodiments, the compositions for genome-scale editing of genetic informa invention is applicable to introducing and balancing of heter tion. ologous recombinant enzyme activity with endogenous metabolism, to limit effects on viability and growth, for BACKGROUND example. In some embodiments, the phenotype relates to 0003. Successful genomic and pathway engineering engineering alterations among one or more proteins, such as, requires that metabolic flux be increased through select path by way of illustration, enzymes, for improved biochemical or ways, while not substantially interfering with viability and/or biophysical properties. growth of the organism, or a desired phenotype. This can be 0007. In various aspects, the invention provides methods especially pertinent for substrates or intermediates of the for pathway engineering, in which metabolic flux is altered desired pathway that are involved in core or primary metabo through one or more intermediates of glycolysis, pentose lism, or for branch intermediates involved in more than one phosphate pathway, TCA cycle, one or more secondary bio pathway. Stephanopoulos, Metabolic Fluxes and Metabolic synthesis pathways (e.g., amino acid or nucleotide biosynthe Engineering, Metabolic Engineering 1, 1-11 (1999). In fact, sis pathway), the mevalonate or non-mevalonate pathway, genetic alterations, or combinations of genetic alterations, pathways involved in Sulfur or nitrogen metabolism, and oth that increase metabolic flux through a desired pathway are ers. The invention relates to, in various embodiments, engi difficult to predict, limiting the usefulness of rational engi neering cells to result in one or more of increased or diversi neering approaches. Kern A, et al., Engineering primary fied carbon Substrate utilization, increased or maintained metabolic pathways of industrial microorganisms, J. Biotech growth rate, modified enzyme activity at metabolic branch nology 129: 6-29 (2007). Further, it is often impractical to points, decreased metabolic flux through one or more com generate random and discrete mutational events in vivo and peting secondary pathways and/or increase in flux through a screen or select for improved metabolic flux or biomolecular desired secondary biosynthetic pathway, balanced cellular function. redox chemistry (e.g., redox cofactor balance), balanced het 0004 Methods are needed for screening the genetic space erologous enzyme activity with the endogenous metabolism, of a host organism to identify changes in endogenous genes including reduction in toxic intermediates, increased resis and/or heterologous recombinant genes that provide tance to environmental (e.g., industrial) conditions, increased improved phenotypes, such as in metabolic flux and balance, recombinant protein production, and increased yield of So as to improve or optimize microbial processes, including desired product. production of desired chemicals and biomolecules at indus 0008. In various aspects, the invention engineers cells trial levels, or bioremediation applications. using one or a combination of recombineering systems. The recombineering systems each offer distinct advantages in SUMMARY OF THE INVENTION engineering cells. In some embodiments, the method pro 0005. In various aspects, the invention provides methods duces a library of mutants cells using a ssDNA recombinase for genomic and pathway engineering. The methods are use system, which may include a single-stranded annealing pro ful in E. coli, as well as bacterial cells that are harder to tein (SSAP), such as the W. Red recombineering system (e.g., genetically manipulate but are otherwise valuable for produc Beta protein) or RecET system (e.g., recT), or homologous tion of chemicals, including Bacillus sp. (e.g., Bacillus sub system, which in Some embodiments offers advantages in tilis), Streptomycetes (e.g., Streptomyces avermitilis, Strep identifying pathways, genes, or regions of genes for alter tomyces coelicolor; Streptomyces lividins, Streptomyces ation, as well as targeting specific regions for genetic diver cinnamomensis, Streptomyces collinus, etc.), Cyanobacteria sification. The W. Red operon encodes ssDNA annealing pro (e.g., Synechocystis spp., Prochlorococcus spp., Nostoc tein Beta, which promotes annealing of single stranded punctiforme, Calothrix spp., Aphanizomenon flos-aquae, oligonucleotides at the lagging Strand of the replication fork. Arthrospira platensis, etc.), and Corynebacteria (e.g., The Red recombineering system, as with other SSAP sys Corynebacteria glutamicum, Corynebacteria ammoni tems, may further involve a deletion, inactivation, or reduc agenes, etc.), among others. The methods are further appli tion in mismatch repair (e.g., deletion, inactivation, or reduc cable in Some embodiments to Eukaryotic cells, such as tion in activity or level of mutS). Such a system is useful for yeasts (e.g., Pichia sp., Saccharomyces sp., Schizosaccharo engineering E. coli and other prokaryotic systems, and may myces sp., Kluyveromyces sp., etc.), filamentous fungi (e.g., be engineered into other species described herein. Specifi Neurospora sp. and Aspergillus sp., Penicillium, etc.), algae cally, an oligonucleotide library designed to Screen for ben (e.g., Botryococcus, Chlorella, Dunaliella, Gracilaria, Pleu eficial mutations (or combinations of mutations) in a target rochrysis, and Sargassum, etc.), and plants. genetic 'space' is introduced into the organism, and a desired US 2016/01 86168 A1 Jun. 30, 2016 phenotype identified. The genetic “space' includes identified introduced into the system. Coupling the site-specific pro target pathways (e.g., a primary metabolic pathway and/or grammable nuclease system to the donor sequence on the one or more secondary competing or biosynthetic pathways), same DNA results in a Scarless method for selecting recom target genes, and the nature and diversity of alterations to binants and obviates the need for an additional selectable Screen, including changes to gene regulatory sequences Such marker. Thus, recombination with the homologous target as promoters and transcriptional enhancer sequences, riboso region mutated at the wild-type locus targeted by the site mal binding sites and other sites relating to the efficiency of specific nuclease permits the cell to escape restriction by the transcription, translation, or RNA processing, as well as cod programmed nuclease system. In other words, recombination ing sequence mutations that control the activity, post-transla with the mutated sequence frees the organism from the tional modification, or turnover of the encoded proteins. Oli genomic instability caused by the programmable site-specific gonucleotide library design strategies to leverage the power nuclease. of this method are described in detail herein. In some embodi 0013 Instill other aspects, the invention provides methods ments, these aspects employ a single stranded DNA anneal for engineering the programmable nuclease system itself by ing protein system with mismatch repair inactivation to iden using the recombineering system to replace or alter the Sub tify target genes to be engineered, that is genes that are sequence of the vector that specifically targets the host optimally up- or downregulated in activity or expression. genomic locus (or loci) Such that a new genomic locus (or Subsequently target genes or sequences are honed with a loci) will be targeted by the programmable nuclease (e.g., more targeted or defined oligonucleotide library, or by a CRISPR/Cas, ZFNs, BurrH binding domain or BulD, derived complementary approach to introduce replacement nucleases, TALEs, and TALENs). sequences by, for example, producing double-strand breaks 0014. In various embodiments, the invention provides in Some cases with homologous recombination. Such alter engineered cells made through the processes described native systems include CRISPR/Cas, ZFNs, Burrh binding herein, and provides methods of producing desired chemical domain or Bul), derived nucleases, TALEs, and TALENs, products through fermentation of the engineered cells. For among others, to introduce double-strand breaks at desired example, the methods and cells may, in various embodiments, location in the host genome to enhance allelic replacement. In produce a biofuel Such as methanol, ethanol, propanol, this manner, the invention uses both rational and random butanol, or isobutanol, or a compound having a C2 to C6 design aspects to engineer cells toward desired phenotypes. carbon skeleton (for example) ethylene, acetate, methacrylic 0009. In some embodiments, the genetic or genomic engi acid, acrylate, lactic acid, isoprene, propanoic acid, hydrox neering systems (e.g., recombineering or site-specific pro ypropanoic acid, propylene, propane, propene, butadiene, grammable nucleases such as Cas, TALENs, ZFNs, or Bulls) butanediol, butanone, butyric acid, butyrolactone, butanal, are inducible or controlled. Such that the engineered strain putrescine, fumarate, malate, levulinic acid, pentanoic acid, remains genetically stable. caproic acid, cyclohexanone, or adipate, among others. In 0010. Other aspects of the invention provides cells that are Some embodiments, fatty acid derivatives, which may serve efficient for recombineering, by targeting the endogenous as valuable long-chain carbon molecules (e.g., alkanes, alk components of the cell, or providing heterologous compo enes) of high energetic value may be produced. In some nents described herein, and Screening for increased recom embodiments, the compound is a product of secondary bineering efficiency. metabolism or biosynthetic pathway, and may be a fatty acid, 0011. In other aspects, the invention is applicable to a natural or unnatural amino acid, lipid, lipopeptide, antibi prokaryotic and eukaryotic organisms that are more difficult otic, nucleotide, pharmaceutical or intermediate thereof, a to genetically manipulate than E. coli. For example, the polynucleotide (e.g. RNA), oraterpene or terpenoid. In some invention allows for target genes or genomic sequence vari embodiments, the compound is a recombinant protein such as ants to be introduced into a recombineering- (e.g., MAGE-) an antibody or insulin. competent organism where engineering can be performed, 0015. Additional aspects and embodiments of the inven e.g. E. coli, using a vector that is compatible for replication in tion will be apparent from the following detailed description. the recombineering or MAGE-competent organism (such as E. coli) and replication in the desired host, or replication in the DESCRIPTION OF THE FIGURES recombineering or MAGE-competent organism and conjuga 0016 FIG. 1 shows shuttle-MAGE plasmid design. The tion into the desired host; and after undergoing one or more Shuttle-MAGE plasmid contains origins of replication and cycles of engineering in the recombineering or MAGE-com selectable marker(s) for the target organism (2u and URA3 in petent organism, the engineered vectors are introduced into orange), a DNA fragment homologous to the region in the the host cell of choice. In various aspects, the vector confers target organism targeted for MAGE mutagenesis (green), and one or more selectable markers for both the recombineering a CRISPR guide RNA expression cassette designed to guide or MAGE-competent organism and the target organism, Such the Cas9 endonuclease to digest the target genome at a speci that following transformation (or transfection, conjugation, fied site (red). The vector backbone (blue) allows the plasmid etc.). Successful transformants can be selected from unsuc to be maintained in MAGE-competent E. coli cells under a cessful transformants. selectable marker. 0012. In some aspects and embodiments of the invention 0017 FIG.2 shows modifying the shuttle-MAGE plasmid employ a vector that encodes a component of a site-specific via MAGE. The repair sequences in the Shuttle-MAGE plas programmable nuclease system (e.g., CRISPR/Cas9, mid were targeted for modification by applying cycles of TALEN. ZFN, Bul), or homologous or analogous system), MAGE with oligos designed to introduce premature stop which is coupled, e.g. in the same vector (e.g., a plasmid), to codons or new fluorescent properties to the target sequences. a donor sequence for a locus targeted by the programmable Panel A shows the ADE2 gene was targeted to be cleaved by nuclease. The donor nucleic acids are not susceptible to cut Cas9 at the designated PAM recognition sequence. Two dis ting by the programmable nuclease, described herein, that is tinct MAGE oligos introduced premature stop codons in the US 2016/01 86168 A1 Jun. 30, 2016 encoding gene to render cells that utilize the given repair in a Substantially continuous process), cells are selected hav sequence to escape Cas9 cleavage unable to express a func ing an improvement in the desired phenotype. tional ADE2 allele. Panel B shows the fluorescent properties 0021 While the invention provides for selecting for any of the Venus-YFP gene introduced into the yeast genome desired phenotype, the desired phenotype can be one or more were altered by the introduction of mutations in the sequence of a change in carbon Substrate utilization, increased cell via MAGE. Oligos were designed to change the Venus-YFP growth rate, increased production of a desired chemical, sequence to that of either the Emerald (Yellow to Green) or redox cofactor balance, reduced production of one or more Cerulean (Yellow to Blue) fluorescent proteins, or to contain undesired byproducts, increased resistance to industrial fer a premature stop codon. The CRISPR gRNA target recogni mentation, and increased recombinant protein production, tion sequence along the YFP target is shown in blue. Panel C among others. shows after cycles of MAGE individual plasmids were 0022. The various steps for diversifying the genetics of the sequenced to confirm that the desired mutations were incor host cell population can target endogenous genes and/or het porated. erologously expressed genes, including enzymes expressed 0018 FIG. 3 shows imaging of yeast colonies to identify as part of a biosynthetic pathway or recombinant proteins for targeted changes. In order to confirm that the desired engi production. neered mutations have been introduced into the target 0023. As cells with the desired phenotype are selected, genomes, colonies of yeast Strains were imaged after having genes altered by the first or Subsequent oligonucleotide librar undergone Shuttle-MAGE manipulation. Panel A shows the ies can be identified by transcriptional (e.g., microarray) or ADE2 Shuttle-MAGE plasmid was transformed into Cas9 translational analysis or by DNA sequencing and compared to expressing BY4741 and BY4733 cells. The resulting cultures a reference genomic sequence (e.g., the starting sequence). were plated onto agar plates and photographed under differ 0024. In some embodiments, the desired phenotype is ent bright-field and fluorescent channels. The colonies that increased production of a desired chemical, and which may appear red have incorporated one of the premature stop codon be the result of a primary metabolic pathway and a down mutations introduced by MAGE on the repair sequence in the stream biosynthetic pathway (which may further comprise at Shuttle-MAGE plasmid. All colonies continue to express the least one heterologously expressed gene in Some embodi Venus YFP protein. Panel B shows the YFP Shuttle-MAGE ments). In some embodiments, the cell expresses a heterolo plasmid was transformed into Cas9-expressing cells. Under gous biosynthetic pathway that alters flux through one or the fluorescent channels, most colonies appear to no longer be more of glycolysis, pentose phosphate pathway, TCA cycle, expressing the Venus YFP fluorescent protein, but rather an MVA or MEP pathway. alternate fluorescent protein, pertaining either to Emerald 0025. In various aspects, the invention provides methods (GFP) or Cerulean (CFP) fluorescent protein. The fluorescent for genomic and pathway engineering. The invention is appli spectra for the encoded YFP and GFP proteins largely over cable to pathway engineering where metabolic flux through a lap, so they appear very similar under the chosen imaging core or primary metabolic pathway is altered (e.g., signifi conditions. cantly altered as compared to wild type, unengineered, or 0019 FIG. 4 shows changing CRISPR gRNAs on the starting strain), including where flux at a metabolic branch shuttle-MAGE plasmid. In order to alter the Cas9 cleavage point is altered. In these or other embodiments, the invention site along the genome (left), a MAGE oligo was designed to is applicable to balance one or more secondary pathways, that change the gRNA sequence in the Shuttle-MAGE plasmid is, to reduce flux from competing secondary pathways while (right). Cycles of MAGE were applied using Oligo 13, which enhancing flux to a desired biosynthetic pathway. In various contained homologous sequences to the regions up and down embodiments, the invention is applicable to introducing and stream of the gRNA recognition sequence on the plasmid. balancing of heterologous recombinant enzyme activity with The resulting library of plasmids is therefore capable of endogenous metabolism, to limit effects on viability and cell digesting and modifying the target genome at multiple sites. growth (for example). In various aspects, the invention pro vides methods for pathway engineering, in which metabolic DETAILED DESCRIPTION OF THE INVENTION flux is significantly altered through one or more intermediates 0020. In various aspects, the invention provides methods of glycolysis, pentose phosphate pathway, TCA cycle, one or for engineering a cell for a desired phenotype. In some more biosynthesis pathways (e.g., for production of natural or embodiments, the method comprises introducing an oligo unnatural amino acids, nucleotides, lipids, fatty acids, antibi nucleotide library into a population of cells, where the cells otics, among others), the MEP or MVA pathway, pathways express a single-stranded annealing protein (SSAP) system involved in Sulfur or nitrogen metabolism, and others. Thus, and/or recombinase that promotes recombination of single the invention relates to, in various embodiments, engineering Stranded oligonucleotides. In some embodiments, the oligo cells to increase one or more of carbon Substrate utilization, nucleotide library targets sequences that control gene expres increase or maintain cell growth rate, modify enzyme activity sion in the cell (e.g., 5' and/or 3' untranslated sequences), at metabolic branch points, decrease metabolic flux through and/or may target protein coding sequences (e.g., including one or more competing secondary pathways, balance cellular start and stop codons). Cells having the desired phenotype redox chemistry (e.g., redox cofactor balance), balance het may then be screened or selected, and genes with altered erologous enzyme activity with the endogenous metabolism, expression as a result of oligonucleotide incorporation can be including reduction in toxic intermediates, increase resis identified for further engineering. Further engineering in vari tance to environmental (e.g., industrial) conditions, and ous embodiments can be conducted by a second oligonucle increase recombinant protein production. otide library designed for diversification of the identified 0026. In some embodiments, the invention engineers cells genes, and/or by targeting at least one gene with a gene through a SSAP system and/or recombinase that promotes editing system, Such as a programmable nuclease as recombination of single stranded oligonucleotides, such as described herein. With each iterative round (or intermittently the Beta protein of the Red recombineering system or the US 2016/01 86168 A1 Jun. 30, 2016

RecT protein of the homologous RecET system, or a homolo after each cycle of transformation, genetic diversity is greatly gous system. In Such embodiments, the host cell expresses the increased in focused regions of the genome according to the ssDNA annealing protein Beta, or derivative or homolog targeted design of the oligonucleotide pool. After Some num thereof. These proteins promote annealing of single stranded ber of cycles of transformation (determined by the size of the oligonucleotides at the lagging Strand of the replication fork. oligomer pool, for example), selection or screening is per These embodiments may further involve a deletion, inactiva formed for the desired genomic characteristic and the process tion, or reduction in a mismatch repair protein. For example, is repeated. In some embodiments, the process is conducted these embodiments can employ a deletion, inactivation, or in a continuous fashion. reduction in activity or level of mutS, or homolog thereof in 0030. In some embodiments, the host cell or strain has one the host organism of choice (see, e.g. U.S. Pat. Nos. 7,144, or more genetic modifications to protect oligos following 734, 7,521,242, and 7,674,621 and US Patent Publication No. entry into the cell. Knocking out four potent ssDNA exonu 2005/0079618, the contents of which are hereby incorporated cleases in E. coli improves oligomediated allelic recombina by reference). This system is useful for engineering E. coli tion frequency when low concentrations of oligos are used and similar bacterial systems. Specifically, an oligonucle (Mosberg, J. A., et al., PloS One, 7(9), e44638). ExoVII is a otide library designed to screen for beneficial mutations (or nuclease that degrades the ends of single-stranded DNA (SS combinations of mutations) in a target genetic 'space' is DNA) oligonucleotides and double-stranded DNA (dsDNA) introduced into the organism by transformation (e.g., by elec cassettes. Removing this nuclease improves both recombina troporation (e.g. Lithium Acetate or PolyEthyleneGlycol), tion frequency and the inheritance of mutations at 3' ends of chemical transformation, ballistic transformation (e.g. gene ssDNA and dsDNA. Removing ExoVII and the set of four gun), pressure induced transformation, mechanical shear exonucleases (Rec.J. ExoI, ExoX, and Lambda Exo) may forces induced, for example, in microfluids, and carbon nano improve recombineering performance. Thus, the host strain tubes, nanotube puncture (such as carbon nanotube arrays), may have a deletion or inactivation in ExoVII, and one or induced natural competence mechanisms of an organism, more (or all) of Rec.J., ExoI, ExoX, and Lambda Exo. merging of protoplasts, and conjugation with Agrobacterium) 0031. In some embodiments, co-selection will be applied of a cell population, and a desired phenotype is identified. to increase the rate at which surviving cells will contain the 0027. The genetic “space' includes selected target path desired mutations. This may be executed by including oligos ways, target genes, and the nature and diversity of alterations that introduce or revert mutations in a counter-selectable to screen, including changes to gene regulatory sequences marker positioned in the genome or on a plasmid along with such as promoters and transcriptional enhancer sequences, the oligos targeting other genomic location(s). This may ribosomal binding sites and other sites relating to the effi include but is not limited to Tolc, as described in (Gregg CJ, ciency of transcription, translation, or RNA processing, as et al. Nucleic Acids Res.42(7):4779-90 (2014), the contents well as coding sequence mutations that control the activity, of which are hereby incorporated by reference). post-translational modification, or turnover of the encoded 0032. In some embodiments, the SSAP system and/or protein. In some embodiments, the oligonucleotide library recombinase that promotes recombination of single stranded targets start and/or stop codons, and splice sites. Alternative oligonucleotides is first used to identify primary and second genomic engineering platforms that may be used, alterna ary pathway targets. For example, transcriptional and/or tively or in combination with the Red or homologous or translational sequences can be broadly disrupted and/or analogous system as described herein, include CRISPR/ enhanced by oligonucleotide design, and the transcriptional Cas9, ZFNs, BurrH binding domain or Bul), derived and/or translational state of cells showing improvement in the nucleases, TALEs, and TALENs. desired phenotype (e.g., chemical production) evaluated to 0028. Thus, in some embodiments, the host cell is an E. identify genes that are frequently upregulated versus genes coli possessing the W. Red recombineering system or the that are frequently downregulated or shut off completely, or RecET system (e.g., the Beta gene or recT gene) and lacking identify frequent or optimal combinations of the above. Tran the mismatch repair gene mutS. The W Red System has been scriptional effects can be induced with the oligonucleotide referred to as Multiplexed Automated Genome Engineering library by exchanging or interfering with gene promoters or (MAGE) and is a process by which the genome of a cell is transcriptional binding sites. Translational effects can be reprogrammed to perform desired functions via a form of induced by the oligonucleotides by enhancing or interfering accelerated, directed evolution (Wang et al., Nature, 460:894 with ribosomal binding sites, such as the Shine-Dalgarno 898 (2009); Church et al., U.S. Pat. No. 8,153,432, the con sequence, or the Kozak sequence, or DNA sequences 5' or 3' tents of which are hereby incorporated by reference in their of the ORF that affect RNA degradation rate, as well as start entireties). During MAGE cycling, Beta proteins recombine and stop codons. These identified genes, optionally including oligos designed to target key genomic regions for highly genes catalyzing adjacent or competing reactions, can be specific mutations. The deletion of mutS may further improve identified by Screening or a selection system with a second recombination efficiency by avoiding the mismatch repair round to identify more finely tuned expression modulation or machinery. amino acid Substitution events that increase product yield. 0029. At each round of transformation, without wishing to 0033 Alternatively or in addition, subsequent rounds be bound by theory, protein Beta binds to, protects, and pro employ CRISPR/Cas9, TALENS, ZFNs, BurrH binding motes Strand annealing of the SSDNA oligomers. This may domain or Bul), derived nucleases, or homologous or anala occur in the lagging strand during DNA replication where the gous systems for refining selected Strains. Such systems can oligomers are thus incorporated into the duplicated genome. be used to induce double-strand breaks (DSB) and increase Without wishing to be bound by theory, the deletion of the homologous recombination efficiency. mismatch repair gene mutS in the recombineering strain pre 0034) For example, a double-strand break (DSB) or vents the reversion of some of the non-homologous genetic single-strand break or nick can be created by a site-specific changes introduced by the ssDNA oligonucleotide pool. Thus nuclease such as a zinc-finger nuclease (ZFN) or TAL effector US 2016/01 86168 A1 Jun. 30, 2016

domain nuclease (TALEN) or BurrH binding domain (Bul))- combined crRNA/tracrRNA system, known as a guide RNA); derived nucleases, or using the CRISPR/Cas9 system with an Jinek, et al. (2012). A programmable dual-RNA-guided DNA engineered crRNA/tracrRNA (or synthetic guide RNA) to endonuclease in adaptive bacterial immunity. Science, 337 guide specific cleavage. See United States Patent Publica (6096), 816-821; Mali, et al. (2013). CAS9 transcriptional tions 2003/0232410; 2005/0208489; 200510026157; 2005/ activators for target specificity Screening and paired nickases 0064.474; 2006/0188987: 2009/0263900; 2009101 17617; for cooperative genome engineering. Nature Biotechnology. 2010/0047805; 2011/0207221, 2011/0301073 and Interna doi:10.1038/nbt.2675; Jiang, et al. (2013). RNA-guided edit tional Publication WO 2007/014275, the disclosures of which ing of bacterial genomes using CRISPR-Cas systems. Nature are incorporated by reference in their entireties for all pur poses. Transgene insertion can be accomplished via homol Biotechnology. doi:10.1038/nbt2508; Dicarlo, at al. (2013). ogy-directed repair (HDR) processes, which require the Genome engineering in Saccharomyces cerevisiae using inserted transgene to include regions of homology to the site CRISPR-Cas systems. Nucleic Acids Research. doi:10.1093/ of insertion (cleavage). Alternatively, targeted integration can nar/gkt135; Gong, etal. (2013). Multiplex Genome Engineer occur by homology-independent non-homologous end join ing Using CRISPR/Cas Systems. Science, 339(6121), 819 ing (NHEJ) DNA repair machinery. Thus, in these embodi 823. doi:10.1126/science. 1231143; Qi, et al.; (2013). ments, the recombineering strain expresses an endogenous or Repurposing CRISPR as an RNA-guided platform for heterologous ZFN, BulD, TALEN, or CRISPR/Cas9. Donor sequence-specific control of gene expression. Cell, 152(5), nucleic acid libraries can be designed for this system as 1173-1183. doi:10.1016/j.cell.2013.02.022: Esvelt, at al. described in detail herein. (2013). Orthogonal Cas9 proteins for RNA-guided gene regulation and editing. Nature Methods, 10(11), 1116-1121. 0035. For example, in certain embodiments, the process doi:10.1038/nmeth.2681; Gaj, et al. (2013). ZFN, TALEN, employs a double-strand break system as described in US and CRISPR/Cas-based methods for genome engineering. 2013/0326645, which is hereby incorporated by reference in Trends in Biotechnology, 31(7), 397-405. doi:10.1016/j. its entirety. In this system, the donor molecules may be inte grated into the endogenous locus via homology-independent tibtech.2013.04.004, the contents of which are hereby incor mechanisms (e.g., NHEJ), and may employ a double porated by reference in their entireties. Stranded donor comprising a transgene or synthetic DNA of at 0038. In some embodiments, the invention provides a least 1 kb in length and nuclease target site(s) 3' and/or 5' of method for engineering a cell for increased recombineering the transgene for in vivo cleavage. The nuclease target site(s) potential (as well as cells provided by Such method), com used to cleave the donorare not re-created upon integration of prising: introducing an oligonucleotide library into said cell, the transgene, for example when a spacer between paired and selecting for increased recombineering potential. target sites is not present in and/or does not exhibit homology Increased recombineering potential may be determined, for to an endogenous locus. The donor molecule may be, for example, by introducing an oligonucleotide directing entry of example, a plasmidora DNA sequence incorporated within a a premature stop codon in a marker gene. plasmid. In certain embodiments, the donor DNA is inte 0039 Recombineering strains may be created through ini grated following nuclease-mediated cleavage of the endog tial genetic modifications to protect and promote ssDNA enous locus. Such processes can employ donor sequences of annealing or homologous recombination efficiency and avoid up to about 20 kb, and in various embodiments employ donor the mismatch repair system. The Suitability of any particular sequences of from about 50 bases to about 10.000 bases, or host cell or strain for recombineering can be assessed using a from about 100 bases to about 5,000 bases, or about 200 bases reporter or selection system. For example, candidate host to about 2,000 bases, or about 200 bases to about 1000 bases. cells or strains are Subjected to cycles of genomic engineering 0036 Double-strand breaks (DSB) or single-strand breaks using an oligo-pool or pool of mutants for recombination (nicks) in the genome of the target cell may be created by any designed to introduce mutations into endogenous or heterolo mechanism. In certain embodiments, the DSB or nick is cre gous genes that control these processes. Exemplary target ated by one or more (e.g., a dimerizing pair of) zinc-finger genes are described below for bacterial and yeast systems for nucleases (ZFNs), fusion proteins comprising a Zinc finger example, and other prokaryotic and eukaryotic counterparts binding domain, which is engineered to bind a sequence are known. The number of initial cycles can be determined within the region of interest, and a cleavage domain or a according to the efficiency of the parent strain and the number cleavage half-domain. In other embodiments, the DSB or of allelic targets. To assess recombineering efficiency, one nick is created by one or more TALE DNA-binding domains cycle is performed with a single oligo designed to replace a (naturally occurring or non-naturally occurring) fused to a premature stop codon in a gene for one or more selection nuclease domain (TALENs). In other embodiments, the DSB marker(s) in the host genome or on a plasmid (e.g., a fluores or nick is created by one or more BurrH binding domains or cent or luminescent reporter protein, or other gene creating an Bul)-derived nucleases, which is engineered to cleave a easily observable or quantifiable phenotype); and after selec sequence within the region of interest. In still further embodi tion for strains capable of Successfully introducing the stop ments, cleavage or nicking is performed using a nuclease codon, quantifying specificity and efficiency of the replace system such as CRISPR/Cas with an engineered crRNA/tracr ment. Promising strains, e.g. those demonstrating more effi RNA or crRNA/tracrRNA combined into a single synthetic cientallelic replacement than Strains from the previous cycle, guide RNA targeting the desired genomic or extra-chromo are then recursively applied to the process. Cycling with Somal sequence. oligos targeting genes that effect ssDNA recombination and 0037. The genetic components of CRISPR/Cas9, as well mismatch repair, or homologous recombination, in the organ as the structural requirements for the crRNA/tracrRNA or ism of choice, generates a diverse population of organisms synthetic guide RNA are described in, for example, PCT/ with a spectrum of recombineering efficiencies. Selection for US2013/032589, publication number: WO2013176772 (de strains with increasingly efficient allelic replacement scribing, inter alia, the use of CRISPR/Cas9 with a single machinery for reintroduction to the pipeline may continue US 2016/01 86168 A1 Jun. 30, 2016 until replacement reaches a plateau, where there is no quan determined by DNA target availability and protein availabil titative improvement in efficiency. ity. RadS9 enhances DNA annealing by RadS2 and increases 0040. In recombineering strains, recombination may be the likelihood of entering the SSA pathway. Overexpression mediated by phage-derived proteins from the Red system or of S. cerevisiae wild-type RadS2 increases recombination RecE/RecT from the Rac prophage of E. coli. The W Red rates of dsDNA, and it has the opposite effect with single recombination functions are encoded by an operon contain strand oligo-mediated AR. When RadS1 and RadS4 are over ing three genes, gamma, beta, and exo, although only the beta expressed together, there is a dramatic increase in oligo gene is required for oligonucleotide incorporation. The mediated AR, which is further elevated in the absence of RecET system is a member of the same superfamily, and the Rad52. This system may be engineered as described above to Red Exo/Beta and RecB/RecT protein pairs are functionally improve the host cell’s efficiency for recombineering. equivalent. Beta and RecT are SSAPs that bind and protect 0045. In this manner, aspects of the invention allow for ssDNA, and Beta is capable of efficient recombination with essentially any host cell to have recombineering potential. In SSDNA oligos by promoting annealing of complementary various embodiments, the cell is a eukaryotic and/or prokary ssDNA at the replication fork. ssDNA recombinases other otic cell, including bacterial, yeast, algal, plant, insect, and/or than or related to Beta and RecT, have been described. non-human mammalian cells, or immortal cell lines. For Sequence analysis of diverse SSAPs and/or recombinases example, the host cell may be Escherichia coli, Saccharomy shows at least six families among at least three evolutionarily ces cerevisiae, Pichia pastoris, Saccharomyces castellii, distinct superfamilies: RadS2-like (of which Red Beta, Sak, Kluyveromyces lactis, Pichia stipitis, Schizosaccharomyces and Erfare members), RadS1-like (e.g., Saka), and Gp2.5- pombe. Chlamydomonas reinhardtii, Arabidopsis thaliana, like, each with distinct sequence profiles and folds. Datta et or Caenorhabditis elegans. In some embodiments the cell is a al., PNAS USA, 105:1626-31 (2008); Lopes, A., Nucleic bacterial cell. Such as Escherichia spp., Streptomyces spp., Acids Research, 38(12), 3952-3962. doi:10.1093/nar/ Zymomas spp., Acetobacter spp., Citrobacter spp., Syn gkg096, which are hereby incorporated by reference in their echocystis spp., Rhizobium spp., Clostridium spp., Coryne entirety. Specifically, recombineering Strains can be engi bacterium spp., Streptococcus spp., Xanthomonas spp., Lac neered as follows. tobacillus spp., Lactococcus spp., Bacillus spp., Alcaligenes 0041. In various embodiments, the host cell or stain spp., Pseudomonas spp., Aeromonas spp., Azotobacter spp., encodes and expresses one or more of a SSAP and/or recom Comamonas spp., Mycobacterium spp., Rhodococcus spp., binase or variant from the three superfamilies described Gluconobacter spp., Ralstonia spp., Acidithiobacillus spp., above. In this context, the term “variant’ means that the Microlunatus spp., Geobacter spp., Geobacillus spp., Arthro variant comprises an amino acid sequence with at least about bacter spp., Flavobacterium spp., Serratia spp., Saccha 50%, at least about 60%, at least about 70%, at least about ropolyspora spp., Thermus spp., Stenotrophomonas spp., 80%, at least about 85%, at least about 90%, at least about Chronobacterium spp., Sinorhizobium spp., Saccha 95%, at least about 96%, at least about 97%, at least about ropolyspora spp., Agrobacterium spp. and Pantoea spp. In 98%, or at least about 99% identity to at least one of the Some embodiments the cell is a Cyanobacterial cell. Such as SSAPs and/or recombinases. Synechocystis spp., Prochlorococcus spp., Nostoc puncti 0042. In some embodiments, yeast strains with higher forme, Calothrix spp., Aphanizomenon flos-aquae, recombineering efficiency with single Stranded oligonucle Arthrospira platensis, etc. The bacterial cell can be a Gram otides are prepared, using a library of oligonucleotides that negative cell such as an E. coli, or a Gram-positive cell Such alter the expression (transcription and/or translation), and/or as a species of Bacillus. In other embodiments, the cell is a coding regions, of one or more (or all) of RadS2, RadS1, fungal cell Such as a yeast cell, e.g., Saccharomyces spp., Rad59, and RadS4, among others genes. Thus, the library of Schizosaccharomyces spp., Pichia spp., Pafia spp., Kluyvero oligonucleotides target for mutations the 5' and/or 3' non myces spp., Candida spp., Talaromyces spp., Brettanomyces coding sequences, intron sequences (including splice sites), spp., Pachysolen spp., Debaryomyces spp., Yarrowia spp., and/or coding sequences of these genes, and the yeast strains and industrial polyploid yeast strains. Preferably the yeast selected for recombineering efficiency as described above. In strain is a S. cerevisiae strain or a Yarrowia spp. Strain. Other Some embodiments, programmable nuclease systems as ref examples of fungi include Aspergillus spp., Pennicilium spp., erenced above are used to target mutations in these genes, for Fusarium spp., Rhizopus spp., Acremonium spp., Neurospora example, as described above by coupling the heterologous spp., Sordaria spp., Magnaporthe spp., Allomyces spp., Usti system with donor DNA on a single vector. lago spp., Botrytis spp., and Trichoderma spp. In other 0043. In yeast, RadS2 may also function independently of embodiments, the cell is an algal cell or a plant cell (e.g., A. the RecA ortholog, RadS1. In yeast, nearly all homologous thaliana, C. reinhardtii, Arthrospira, P. tricomutum, T. recombination pathways begin with resection of dsDNA to suecica, P. Carterae, P tricomutum, Chlorella spp., Such as generate 3'-terminated ssDNA, followed by the binding of Chlorella vulgaris). Target cells can include transgenic and RPA and Rad52, and its paralog RadS9. RAD52 binds ssDNA recombinant cell lines, including Chinese Hamster Ovary during recombination and also shows a quaternary organiza cells (CHO). tion similar to those of RecT/RedBand ERF, and may be used 0046. In various embodiments, the host cell or strain, in in the invention in various embodiments. addition to having a SSAP system and/or recombinase that 0044) The RPA-RadS2-Rad59-ssDNA complex can par promotes recombination of single stranded oligonucleotides ticipate in either RadS1-ssDNA filament formation and the as described, has one or more nucleic acids for inhibiting a canonical gene conversion pathway or RadS2-mediated (and mismatch repair system. While these systems can be inacti RadS1-independent) single-strand annealing. This choice is vated by a more permanent genetic deletion or mutation primarily controlled by RadS1, but is moderated by RadS9 event, alternatively, the systems can be controlled by and other cellular proteins. The competition is dynamic and expressed inhibitor nucleic acid, which in Some embodiments reversible, and the pathway chosen for DSB repair is likely is inducible to render recombineering an inducible pheno US 2016/01 86168 A1 Jun. 30, 2016

type. In other embodiments, inhibitory nucleic acids are not oligonucleotides may be designed to block expression of a encoded by the cell, but are provided exogenously (e.g., tran DNA or RNA target by binding to the target and halting siently) to allow recombineering to take place. Inhibitory expression at the level of transcription, translation, or splic nucleic acids include, but are not limited to, antisense oligo ing. The antisense oligonucleotides can be complementary nucleotides, antagomirs, and RNAi-related sequences (e.g., nucleic acid sequences, or Substantially complementary short hairpin RNA (shRNA), microRNA (miRNA) and small sequences, designed to hybridize under Stringent conditions interfering RNA (siRNA)) that target mismatch repair genes to a mismatch repair gene. In some instances, one or more within a target cell and thereby decrease expression of the inhibitory nucleic acids can be RNAi-related sequences, mismatch repair gene in the cell. Mismatch repair genes that including but not limited to a small interfering RNA can be targeted includebut are not limited to, for example, one (“siRNA') or short hairpin RNA (“shRNA'). The interfering or more of Msh2, Msh3, Msho, Mlh1, Mlh2, and/or Pms1. RNA can be assembled from two separate oligonucleotides, 0047. The mismatch repair (MMR) system is primarily responsible for correcting errors following replication, but it where one strand is the sense strand and the other is the also directly takes part in homologous recombination by antisense strand, wherein the antisense and sense Strands are rejecting recombination partners with insufficient homology. self-complementary (i.e., each strand comprises nucleotide The proteins responsible for initiation of E. coli mismatch sequence that is complementary to nucleotide sequence in the repair are MutS and MutL, which function as homo-oligo other Strand; Such as where the antisense strand and sense mers. MutS is responsible for mismatch recognition and strand form a duplex or double stranded structure); the anti MutL serves to interface mismatch recognition by MutS to sense strand comprises nucleotide sequence that is comple activation of downstream activities. Eukaryotes have at least mentary to a nucleotide sequence in a target nucleic acid two MutS heterodimers that share MSH2 as a common sub molecule or a portion thereof (i.e., an undesired gene) and the unit: MSH2-MSH6 and MSH2-MSH3. The MSH2-MSH6 sense Strand comprises nucleotide sequence corresponding to heterodimer mainly recognizes single nucleotide Substitu the target nucleic acid sequence or a portion thereof. Alterna tions and small loops of 1 or 2 bases, while the MSH2/MSH3 tively, interfering RNA is assembled from a single oligo pair has greater affinity for larger loops of 2-5 unpaired nucle nucleotide, where the self-complementary sense and anti otides. Three eukaryotic MutL heterodimeric complexes have sense regions are linked by means of nucleic acid based or been identified with MLH1 serving as a common subunit: non-nucleic acid-based linker(s). The interfering RNA can be MLH1-PMS2, MLH1-PMS1, and MLH1-MLH3. MLH1 a polynucleotide with a duplex, asymmetric duplex, hairpin PMS2 is the primary MutL activity inhuman mitotic cells and or asymmetric hairpin secondary structure, having self supports repair initiated by either MutS heterodimer. complementary sense and antisense regions, wherein the anti 0048 Avoidance of the MMR system in E. coli recom sense region comprises a nucleotide sequence that is comple bineering is Substantially more effective in Strains lacking mentary to a nucleotide sequence in a separate target nucleic MMR machinery, at the cost, or benefit depending on per acid molecule or a portion thereofand the sense region having spective, of higher overall mutation rates. See, e.g., and US nucleotide sequence corresponding to the target nucleic acid Patent Publication No. 2005/00796.18, the contents of which sequence or a portion thereof. The interfering RNA can be a are hereby incorporated by reference. Indeed temporary Sup circular single-stranded polynucleotide having two or more pression of MMR is an effective strategy for enhancing gene loop structures and a stem comprising self-complementary editing efficiency in many cells. Using short-hairpins to Sup sense and antisense regions, wherein the antisense region press MSH2 expression allows for large increases in allelic comprises nucleotide sequence that is complementary to recombination efficiency. Transient suppression of MSH2 by nucleotide sequence in a target nucleic acid molecule or a shRNA is very effective for base substitutions, particularly portion thereof and the sense region having nucleotide for the simultaneous substitution of 3-4 bases rather than 1 or sequence corresponding to the target nucleic acid sequence or 2. Transient knockdown of the downstream MMR gene, a portion thereof, and wherein the circular polynucleotide can Mlh1, rendered ES cells permissive for oligo-mediated single be processed eitherina target cell to generate an active siRNA base pair alterations. Other factors at the interface of homolo molecule capable of mediating RNA interference. gous recombination and mismatch repair may also markedly 0050. In some instances, the interfering RNA coding contribute to increased allelic recombination efficiency. For region encodes a self-complementary RNA molecule having example, oligo-mediated targeted mutagenesis by RadS 1/54 a sense region, an antisense region and a loop region. Such an in early mouse embryos is enhanced by inhibition of the RNA molecule when expressed desirably forms a “hairpin' homologous recombination partners Ku70/86. Numerous structure, and is referred to herein as an “shRNA. The loop other interactions exist that could potentially offer subtle or region is generally between about 2 and about 10 nucleotides even dramatic improvements. For example, disassembly of in length. In some embodiments, the loop region is from about the RadS1-ssDNA filament is controlled by the Srs2 helicase 6 to about 9 nucleotides in length. In some embodiments, the and RadS2-mediated annealing between divergent homolo sense region and the antisense region are between about 15 gous sequences is subjected to heteroduplex rejection by the and about 23 nucleotides in length. Following post-transcrip Sgs1 helicase. The connection between these two processes tional processing, the Small hairpin RNA is converted into a can also explain, without wishing to be bound by theory, why siRNA by a cleavage event mediated by the enzyme Dicer, deletion of RAD54, which promotes stabilization of RadS1 which is a member of the RNase III family. The siRNA is then ssDNA filaments and DNA strand invasion, also increases capable of inhibiting the expression of a gene with which it SSA efficiency. Furthermore, the RadS2 SSA recombination shares homology. For details, see Brummelkamp et al., Sci pathway also depends on MSH2, MSH3 and numerous other ence 296:550-553, (2002); Lee etal, Nature Biotechnol., 20, components. 500-505, (2002); Miyagishi and Taira, Nature Biotechnol 0049. In some embodiments one or more inhibitory 20:497-500, (2002); Paddison et al. Genes & Dev. 16:948 nucleic acids can be antisense oligonucleotides. Antisense 958, (2002); Paul, Nature Biotechnol, 20, 505-508, (2002); US 2016/01 86168 A1 Jun. 30, 2016

Sui, Proc. Natl. Acad. Sci. USA, 99(6), 5515-5520, (2002); cleases in E. coli improves oligomediated allelic recombina Yueta). Proc NatlAcadSci USA99:6047-6052, (2002). tion frequency when low concentrations of oligos are used. 0051. The target RNA cleavage reaction guided by siR ExoVII has been identified as a nuclease which degrades the NAS is highly sequence specific. In general, siRNA contain ends of single-stranded DNA (ssDNA) oligonucleotides and ing a nucleotide sequences identical to a portion of the target double-stranded DNA (dsDNA) cassettes. Removing this nucleic acid (i.e., a mismatch repair gene) are preferred for nuclease may improve both recombination frequency and the inhibition. However, 100% sequence identity between the inheritance of mutations at 3' ends of ssDNA and dsDNA. siRNA and the target gene is not required. Thus the invention Removing ExoVII and the set of four exonucleases (Rec.J. has the advantage of being able to tolerate sequence varia Exol, ExoX, and Lambda Exo) improves recombineering tions that might be expected due to genetic mutation, Strain performance. polymorphism, or evolutionary divergence. For example, 0054. In some embodiments, the host cell or strain pro siRNA sequences with insertions, deletions, and single point vides for controlled activation/termination (e.g. expression of mutations relative to the target sequence have also been found the machinery necessary for recombineering, or double to be effective for inhibition. Alternatively, siRNA sequences Strand break or nicking by the programmable site-specific with nucleotide analog Substitutions or insertions can be recombinase systems described herein, can be controlled). effective for inhibition. In general the siRNAs must retain Control of machinery that Suppresses the mismatch repair specificity for their target, i.e., must not directly bind to, or mechanisms of the host cell provides for genomic stability directly significantly affect expression levels of transcripts before and after the recombineering process. In some other than the intended target. embodiments, expression of constructs can be induced by 0052. In some embodiments, a one or a plurality of inhibi chemical orthermal means and can remain unexpressed when tory nucleic acids are used to target one or more of Msh2, not induced (or vice versa). In some embodiments, the recom Msh3, Msho, Mlh1, Mlh2, Mlh 3, and/or Pms1, in Saccha bineering phenotype or programmable site-specific nuclease romyces cerevisiae, Pichia pastoris, Saccharomyces castellii, phenotype is reversible, that is, constructs can be removed Kluyveromyces lactis, Pichia stipitis, Schizosaccharomyces after performing the recombineering process. In the case pombe. Escherichia coli, Chlamydomonas reinhardtii, Ara where the construct is to be maintained as a plasmid or epi bidopsis thaliana, Caenorhabditis elegans, or mammalian Some with a selectable marker, the construct can be removed (e.g., non-human mammaliancells). For example, a construct by growth in non-selectable media as is standard practice for for use in Saccharomyces cerevisiae can include one or a the target organism. In the case where the construct is to be plurality of inhibitory nucleic acids that target Msh2 (NP integrated into the host genome, the device may include 014551.1), Msh;3 (NP 010016.2), Msho (NP 010382.10), sequence elements to allow for rapid removal (e.g., flanking M1h1 (NP 013890.1), Mlh3 (NP 015161.1), and/or Pms 1 (NP loXP sequence). 014317.2). In some instances, constructs can include one or a 0055 Expression control sequences suitable for regulat plurality of inhibitory nucleic acids that target different ing expression of a SSAP system and/or recombinase that regions within the same gene. For example, in the case of promotes recombination of single Stranded oligonucleotides, Saccharomyces cerevisiae, constructs can include one or a programmable nucleases, and optionally one or more inhibi plurality of inhibitory nucleic acids against Msh2 (NP tory nucleic acids, can include a promoter and/or enhancer 014551.1), Msh;3 (NP 010016.2), Msho (NP 010382.10), sequence. The promoter and/or the enhancer can be inducible M1h1 (NP 013890.1), Mlh3 (NP 015161.1), and/or Pms 1 (NP (e.g. chemically or physically regulated). A chemically regu 014317.2). In an equivalent manner, targeting of the follow lated promoter and/or enhancer can, for example, be regu ing genes can also occur: lated by the presence of alcohol, tetracycline, a steroid, or a

Target gene Target cell Msh? Msh, Mshes MIh1 M3 Pms1.2 Saccharomyces NP 014551.1 NP 010016.2 NP 010382.1 NP 013890.1 NP O15161.1 NP O14317.2 cerevisiae Pichia pastoris XP 0024907 75.1 XP 002490502.1 XP 002490975.1 XP OO2491051.1 XP OO1388O13.2 XP OO2493530.1 Saccharomyces CCC67425.1 CCC7005.1.1 CCC6848.2.1 CCC69671.1 CCC6911.8.1 CCCF 1165.1 castei Kluyveromyces XP 4552O2.1 XP 453028.1 XP 452992.1 XP 53504.1 XP 452646.1 XP 452705.1 iactis Pichia stipites XP OO1386399.2 XP OO1384.1912 XP OO1387.139.2 XPOO1384344.2 XP OO1388O13.2 XP OO1384508.2 Schizosaccharomyces XP 001713136.1 NP 593952.1 NP 588344.1 NP 5961.99.1 NP 594417.1 pombe Escherichia coi NP417213.1 Chlamydomonas XP OO1698.121.1 XP OO1689901.1 XP OO1690102.1 XP OO1692227.1 reinhardtii Arabidopsis NP 566804.3 NP 194284.2 NP 192116.1 NP 567345.2 NP 195277.5 NP 567236.1 thaiana NP 850630.1 NP 189075.2 Cacnorhabditis NP 4912O2.1 NP 491163.1 NP 499796.2 NP 505933.1 NP 505933.1 elegans Mits musculus NP 032654.1 NP O34959.2 NP 034960.1 NP 081086.1 NP 78.0546.1 NP 032912.2

0053. In some embodiments, the host cell or strain has one metal, to name but a few. A physically regulated promoter or more genetic modifications to protect oligos following and/or enhancer can, for example, be regulated by environ entry into the cell. Knocking out four potent ssDNA exonu mental factors, such as temperature and light. In some US 2016/01 86168 A1 Jun. 30, 2016

instances, expression control sequences can include copper target genes to be introduced into E. coli using a vector that is and nickel dependent promoters such as the Cyc6 promoter compatible for replication in E. coli and the desired host, and (Quinn et al., Eukaryotic cell. 2:995-1002 (2003)). In some after undergoing rounds of engineering in E. coli, the engi instances, expression control sequences can include light neered vectors are introduced in the host cell of choice. For induced expression control systems that include. e.g., the example, in these embodiments the method comprises pro Cab-1 promoter. In some instances, expression control viding a vector Suitable for replication in a target species (e.g. sequences can include tetracycline-controlled systems, any of the cells disclosed herein) and suitable for replication including Tet-Off and Tet-On (Bujard et al., PNAS USA, in a second species (e.g. any of the cells disclosed herein). The 89:5547-51 (1992)). second species expresses a SSAPSystem and/or recombinase 0056. In some embodiments, the host cell or strain con that optionally promotes annealing of single stranded oligo trols localization of recombineering or programmable nucleotides at the lagging strand of the replication fork, or the nuclease effectors within the cell, to thereby control the pro second species expresses a gene editing system, wherein the cess in an on or off fashion. For example, the ligand-binding vector comprises a target polynucleotide for engineering. The domain (LBD) of the estrogen receptor (ER) can be used to vector is introduced into the second species under conditions regulate the localization and activity of nuclear proteins in suitable for diversification of said target polynucleotide by yeast and mammalian cells. Nuclear proteins containing the the SSAP system and/or recombinase, and the vector library ER LEBD are retained in the cytoplasm until activated by isolated and introduced into said target species. The second estradiol or the functional estrogen antagonists tamoxifen species may be E. coli, and the target species can be a slow (TAM) or 4-hydroxy-tamoxifen (4OHT). Upon binding, the growing organism. In some embodiments, the target species ligand displaces Hsp90 and facilitates correct folding of the is S. cerevisiae oran actinomycetes and the second species is released fusion protein, which activates the LBD fused E. coli, or the target species is a plant and the second species nuclear protein and allows translocation to the nucleus. Sev is an agrobacter. eral ER ligand variants with different activation mechanisms 0060. In some embodiments, genome engineering for the are known. The mouse ER LEBD mutant G525R and corre target organism is conducted in a MAGE-competent recom sponding human mutant G521R (ERT) exhibit roughly a bineering strain, for example Such as an E. coli Strain 1000-fold reduction in 17 B-estradiol binding affinity com described herein, anlocus (or library thereof) exported to pared to wildtype, yet retain normal affinity for TAM and target cells (e.g., non-recombineering or MAGE-competent 4OHT. The 4OHT affinity of the human ER LBD mutant strains). In certain embodiments, the invention provides a ERT2 (G400V/M543A/L544A) is approximately 4-fold method formultiplex genomic alteration of a target cell popu higher than that of ERT. In addition to the Gal4 transcription lation, comprising: (a) generating a combinatorial vector factor fusion to ER and VP16 (GEV), ectopic DNA enzymes library in a recombineering cell population; and (b) transfer such as Cre, Flp and I-Sce have successfully been controlled ring the combinatorial vector library to a target cell popula by fusion with ERT and other nuclear hormone receptors. tion. While genome engineering methods such as MAGE, These systems can be adapted for host cells of choice, includ CRISPR/Cas9, BulDs, ZFNs, TALEs, and TALENs are appli ing yeast. cable to many diverse species, multiplex application of these 0057. In some embodiments, ER LEBD and mutants fused technologies can behindered in Some organisms by the length to other yeast nuclear proteins would elicit the same proper of time required to execute the sequential rounds of engineer ties of control. For example, fusing these components to ing necessary to accumulate the combinatorial diversity in the various mutant SSAP or SSAP enabling genes allows consti loci of interest. For example, organisms such as Actino tutive expression, whereby the proteins remain inactive (and mycetes (e.g. Streptomyces spp.), are relatively slow growing non-physiological) in the cytosol until activated prior to and laboratory techniques used to perform genetic manipula transformation. Furthermore, an inducible protein degrada tions may take days or weeks. To facilitate application of tion system using the GEV system to activate expression of multiplex genome engineering techniques in slow growing or the Tobacco EtchVirus (TEV) protease is useful in the present difficult to manipulate organisms. Such as the Actinomycetes, invention. TEV specifically degrades proteins with the N-de the present invention provides methods and compositions to gron peptide sequence. With expression of TEV under tight elaborate the diversity indirectly in a faster growing and control of the GEV system. MMR and/or Non-Homologous easier to manipulate organism, Such as E. coli, via a shuttle End Joining (NHEJ) pathway members with N-degron system. By elaborating the diversity in the shuttle system sequences can be degraded concomitant with SSAP activa within the facile E. coli host, then introducing the generated tion. shuttle library into the target organism, extended sequential 0.058. In these or alternative embodiments, the host cell or cycles in the non-facile target organism are avoided. Such strain can include one or more nucleic acids encoding one or methods and compositions are applicable to a variety of mul more CRISPR pathway components e.g., operably linked to tiplex genome engineering techniques (e.g. MAGE, CAGE, expression control sequences. In some instances, expression CRISPR/Cas9, BulDs, ZFNs, TALEs, and TALENs). In some control sequences for proteinbeta, one or a plurality of inhibi embodiments the genetic diversity at the desired locus is tory nucleic acids, and/or RNAi and/or CRISPR machinery synthesized and not elaborated with a technique such as can be distinct and independently controlled. In some MAGE, then cloned directly into the vector (e.g., a plasmidor instances, expression control sequences for protein beta, one virus) using standard methods. In still other embodiments the or a plurality of inhibitory nucleic acids, and/or RNAi and/or genetic diversity is synthesized and cloned directly into the CRISPR machinery can be the same or can be induced via the vector. In still other embodiments the DNA is then further same signal. elaborated with a technique such as MAGE. 0059. In some aspects, the invention is applicable to 0061. In some embodiments, the vector possesses one or prokaryotic organisms that are more difficult to genetically more selectable markers such that the vector may be selected manipulate than E. coli. For example, the invention allows for for in both the recombineering organism and the target organ US 2016/01 86168 A1 Jun. 30, 2016

ism. In still other embodiments all or a portion of the site embodiments, the tracrRNA is also expressed from the specific programmable nuclease system (e.g., CRISPR/Cas9. genome or separate from the plasmid and only the crRNA is TALEN. ZFN, Bul), or homologous or analogous system) is encoded on the plasmid. In still other embodiments, the plas encoded and coupled, e.g. in the same vector. For example, mids encode one or more TALENs, ZFNs, Bus, or analo when using the CRISPR/Cas9 system the components of the gous system, each further providing a donor nucleic acid for site-specific programmable nuclease system comprises the introduction into the targeted region of the host genome. In gRNA or crRNA and tracrRNA. In some embodiments, the this manner, desired donor nucleic acids targeting the particu gRNA (e.g. synthetic gRNA) is present on the same vector. In lar site can be introduced into the host cell and screened or some embodiments, the crRNA is present on the same vector. selected for desired phenotype. In various embodiments, the In some embodiments, the crRNA and tracrRNA are present donor nucleic acids are not susceptible to cutting by the Cas9 on the same vector. In some embodiments, the Cas9 is present and crRNA/tracrRNA (or synthetic guide RNA), or analo on the same vector. In some embodiments, the same vector gous programmable nuclease described herein, that is intro encodes one or more TALENs programmed to cut the target duced into the system. The library of vectors may thereby sequence. In some embodiments, the same vector encodes allow for the screening of any number of variant donor one or more ZFNS programmed to cut the target sequence. In nucleic acids, such at least about 10, about 10, about 10, Some embodiments, the same vector encodes one or more about 10, about 10, about 107, about 10, about 10, about BulS programmed to cut the target sequence. In some 10" or more, without an additional or integrating selectable embodiments, the site-specific programmable nuclease sys marker to select for recombination events. In some embodi tem is directly tethered on the same DNA to the repair or ments, the library varies one or more (or all) of promoter donor sequence that is elaborated with a multiplex genome sequences, ribosomal binding sequences, coding region engineering technique (e.g. MAGE, CAGE, CRISPR/Cas9, variations, silent codon variations, synthetic scaffold compo Bulls, ZFNs, TALEs, and TALENs) (e.g. there is roughly a nents, and protein tags to select for optimal expression, func 1:1:1 ratio of DNA encoding selectable marker for the target tion, and/or activity of the target. organism, the programmable nuclease designed to cut the organism genome and the repair or donor DNA). Also, in 0063 Cloning methods are known in the art and include, Some embodiments, there may be one or more (e.g. 1, or 2, or by way of non-limiting example, fusion PCR and assembly 3, or 4, etc.) of the site-specific programmable nuclease sys PCR see, e.g. Stemmer et al. Gene 164(1): 49-53 (1995), tem and repair or donor sequence on the same vector (e.g. one inverse fusion PCR see, e.g. Spiliotis et al. PLoS ONE 7(4): or more gRNA and donor sequence on the same vector (op 35407 (2012), site directed mutagenesis see, e.g. Ruvkun et tionally also with Cas9 on the same vector), one or more al. Nature 289(5793): 85-88 (1981). Gibson assembly (see, crRNA and donor sequence on the same vector (optionally e.g. Gibson et al. Nature Methods 6 (5): 343-345, (2009) the also with Cas9 on the same vector), one or more crRNA and contents of which are hereby incorporated by reference in tracrRNA and donor sequence on the same vector (optionally their entirety), Quickchange see, e.g. Kalnins et al. EMBO also with Cas9 on the same vector), one or more TALENs 2(4): 593-7 (1983), Gateway see, e.g. Hartley et al. Genome programmed to cut the target sequence and donor sequence Res. 10(11):1788-95 (2000), Golden Gate see, e.g. Engler et on the same vector, one or more ZFNS programmed to cut the al. Methods Mol Biol. 1116:119-31 (2014), restriction digest target sequence and donor sequence on the same vector, and and ligation including but not limited to bluntend, Sticky end, one or more Bulls programmed to cut the target sequence and and TA methods see, e.g. Cohen et al. PNAS 70 (11): 3240-4 donor sequence on the same vector). In various embodiments, (1973). Such vectors, each targeting a unique genomic locus, may be 0064. In some embodiments, the shuttle vector encodes an transformed together, optionally in a cyclical manner in a origin of replication suitable for both the host where the similar way as with MAGE (as described herein). In some combinatorial vector library is generated (e.g., E. coli) as well embodiments, the systems described herein allow selection as an origin of replication of one or more target organisms for the vector DNA, and against wild type genomic locus where the desired mutations are to be introduced. Illustrative being targeted by the programmable nuclease, by providing origins of replication are known in the art (see, e.g., Bryant et relief from genome cutting through repair by the donor DNA al., J Exp Bot., 52(355):193-202 (2001); Edward et al., Basic that contains the desired mutation(s). Virology Third Edition, Blackwell publishing, ISBN 1-4051 0062. This approach allows for a scarless method for 4715-6 (2007); Mott and Berger, Nat. Rev. Microbial., 5 (5): selecting recombinants and obviates the need for additional 343-54 (2007); Huberman et al., Cell, 6: 51(3):473-81 or genome integrating selectable markers. In this case, recom (1987); Brewer and Fangman, Cell, November 6; 51(3):463 bination with the homologous target region mutated at the 71 (1987); Kitai et al., J. Virol. 79(10): 5933-5942 (2005): wild-type locus targeted by the site-specific nuclease permits Kelman, Trends Microbial., 12:399-401 (2004); Nasheuer et the cell to escape restriction by the programmed nuclease al., Prog. Nucleic Acid Res. Mol. Biol., 72: 41-94 (2002), the system. In other words, recombination with the mutated contents of which are hereby incorporated by reference in sequence frees the organism from the genomic instability their entireties). caused by the programmable site-specific nuclease. Thus, in 0065. In some embodiments, a programmable nuclease is Some embodiments, a library of plasmids is introduced into a employed in the recombineering or MAGE-competent organ population of host cells, the plasmids encoding and allowing ism, or organism where the combinatorial shuttle vector for expression of Cas9 or homologous or analogous CRIPSR library is generated, in order to eliminate those vectors where enzyme, and a crRNA/tracrRNA or synthetic guide RNA mutations were not introduced into the desired target targeting a region of the host cell genome. In still other sequence of the target organism through the course of engi embodiments. Cas9 is expressed from the genome or separate neering. Thus, the final vector library produced is Substan from the plasmid and the plasmids express only a crRNA/ tially enriched for possession of mutated target sequences to tracrRNA or a single synthetic guide RNA. In still other be introduced into the target organism. US 2016/01 86168 A1 Jun. 30, 2016

0.066. In some embodiments, the shuttle vector encodes an duced by MAGE (for example) or synthetic DNA method, origin of replication allowing for tunable control of copy designed to target a specific locus of the genome of the Acti number such as pETcoco-1 or pBTcoco2, such that when nomycete spp., and/or encodes one or more genes conferring creating the combinatorial library, a lowerplasmid copy num function necessary or useful for one or more cassettes to ber can be utilized to elaborate the genetic diversity at the recombine with its target locus in the genome of the Actino desired locus (as described herein). As such, the proportion of mycete spp. In some embodiments, the cassettes are separated vectors within the cell population undergoing allelic replace by one or more restriction digest sites that enable digestion by ment with an oligonucleotide is increased at each cycle. Fur an endogenous restriction endonuclease, (e.g., Sau3239I. thermore, the copy number can be increased prior to transfer Stul, or ScoI) or an exogenous restriction endonuclease to the target organism, in order to increase yield. encoded by one or more of the cassettes, under control of an 0067 v RED-mediated (or functionally similar) genetic inducible or constitutive promoter. manipulation of a compound-producing Actinomycetes may 0072. In some embodiments, a cassette may possess one or be undertaken. The strategy employs E. coli as a Surrogate to more genetic markers that can be selected in the Actinomycete enable recombineering with the RED cassette. The E. coli spp. In various embodiments, the marker enables selection of strain may carry a plasmid expressing W RED, and a vector the vector prior to integration and/or the marker is capable of containing one or more target genes or regions in the Actino integrating into the genome of the Actinomycete spp. together mycetes or other non-recombineering cell. Recombineering with the region of homologous DNA, with one or more inser is used to perform the replacement with an oligo library tions, deletions, or mutations introduced by MAGE or syn targeting the Actinomycetes gene of interest within the vector. thetic DNA method. In some embodiments, the marker can be The vector may then be purified and transferred and/or con recycled for use in Subsequent modifications of the genome of jugated or used in any other Suitable transferring technique. the Actinomycete spp. by, for example, flanking the marker The genetic exchange in Actinomycetes is Subsequently sequence with site-specific recombinase recognition targets achieved by homologous recombination between the chro such as FRT or loxP for example, that can be excised from the mosomal locus and the recombinant vector following conju genome following expression of Flp or Cre recombinase, gation. respectively, using standard methods. 0068. The inclusion of oriT (RK2) allows conjugation to 0073. In some embodiments, the cassette contains one or introduce the recombineering-modified vector into an Acti more genes, under control of an inducible, repressible, or nomycete (e.g. Streptomyces coelicolor). Conjugation is constitutive promoter, that render the recipient strain more efficient than transformation of protoplasts and is improved in homologous recombination efficiency, e.g.: the w readily applicable to many actinomycetes. The potent methyl RED cassette from phage A: RecB/T; homologs of the RadS2, specific restriction system of Actinomycetes (e.g. Streptomy Red-beta, Erf, Sak, RadS1 superfamily, and/or endogenous or ces) is circumvented by passaging the vector DNA through a exogenous analogs and Beta from E. coli, EF2132 from E. methylation-deficient E. coli host such as, for example, faecalis, Orf from L. pneumophila, SO65 from V cholera, ET12567 and various Dam- Dcm-strains. Alternatively, the plu2935 from Pluminescens, RecT from E. coli, OrfA8 from recombineering strain itself may be made methylation-defi L. monocytogenes, Orf245 from L. lactis, GP35 from B. sub cient. tilis, GP61 from M. Smegmatis, GP20 from S. aureus and/or 0069 Vectors with an oriT (RK2) site are transmissable in endogenous or exogenous analogs. trans by puB307 in E. coli or the non-transmissible 0074. In one embodiment, multiple vectors are used for pUZ8002, which lacks a cis-acting function. To adapt the construction. In some embodiments, one or more vectors procedure of W RED-mediated recombination for Actino comprise a sequence allowing conjugation with Actino mycetes (e.g. Streptomyces), cassettes were constructed that mycete spp. (e.g. Streptomyces). Such as oriT, and/or a select can be selected both in E. coli and in Actinomycetes (e.g. able marker and origin or replication for E. coli, and/or a Streptomyces). After a single disruption with an oriT-contain CaSSette. ing cassette, further disruptions can be performed on the same 0075. In some embodiments, one or more vectors option vector using oriT-free cassettes containing alternative selec ally further comprises a sequence which encodes a program tive markers. mable site-specific nuclease system (e.g., TALEN, Bul), or 0070 Thus, a MAGE-competent strain of E. coli can CRISPR/Cas9) as described above, or one or more compo readily be used to develop a combinatorial library of Actino nents of Such a system, Such as a tracrRNA, crRNA, or syn mycetes (e.g. Streptomyces, S. Coelicolor) vectors targeting thetic guide RNA, targeting the wild-type locus of a region of one or multiple Actinomycetes (e.g. Streptomyces, S. coeli the Actinomycete spp. genome targeted for diversification by color) genomic loci. The entire E. coli library would subse the cassette conferring the homologous sequence, as quently be conjugated with Actinomycetes (e.g. Streptomy described herein, where the site-specific nuclease may be ces, S. coelicolor) as outlined herein. under control of an inducible, repressible, or constitutive 0071. The combinatorial vector library can be constructed promoter. In some embodiments, the cassette may be engi in multiple ways to facilitate multiplex genome engineering neered to create a diverse combinatorial vector library using of diverse cells as described herein. In one embodiment, a the methods described herein and/or by including synthesized vector possessing a sequence allowing conjugation with DNA Streptomyces, such as oriT, a selectable marker and origin of 0076. In some embodiments, the cassette possesses one or replication for E. coli and one or multiple cassettes is used for more genetic markers that can be selected in the Actinomycete construction. In some embodiments, each cassette may be spp. Such that, for example, the marker enables selection of engineered by MAGE (e.g., SSAP system and/or recombi the vector prior to integration; or the marker is capable of nase) to create a diverse combinatorial vector library. In some integrating into the genome of the Actinomycete spp. together embodiments, a cassette is a region of homologous DNA, with the region of homologous DNA, with one or more inser with one or more insertions, deletions, or mutations intro tions, deletions, or mutations introduced by MAGE (for US 2016/01 86168 A1 Jun. 30, 2016

example) or synthetic DNA method. In various embodiments, domonas reinhardtii, Arabidopsis thaliana, or Caenorhabdi the marker can be recycled for use in Subsequent modifica tis elegans. In some embodiments the cell is a bacterial cell, tions of the genome of the Actinomycete spp. by flanking the Such as Escherichia spp., Streptomyces spp., Zymonas spp., marker sequence with site-specific recombinase recognition Acetobacter spp., Citrobacter spp., Synechocystis spp., targets such as FRT or loxP for example, that can be excised Rhizobium spp., Clostridium spp., Corynebacterium spp., from the genome following expression of Flp or Cre recom Streptococcus spp., Xanthomonas spp., Lactobacillus spp., binase, respectively. Lactococcus spp., Bacillus spp., Alcaligenes spp., Pseudomo 0077. In some embodiments, conjugation can then be used nas spp., Aeromonas spp., Azotobacter spp., Comamonas to efficiently introduce the modified DNA library into Acti spp., Mycobacterium spp., Rhodococcus spp., Glucono nomycetes using previously described techniques (see, e.g., bacter spp., Ralstonia spp., Acidithiobacillus spp., Microlu Matsushima, incorporated by reference in its entirety). In natus spp., Geobacter spp., Geobacillus spp., Arthrobacter some embodiments, the modified DNA library can be intro spp., Flavobacterium spp., Serratia spp., Saccharopolyspora duced by means known in the art (by way of non-limiting spp., Thermus spp., Stenotrophomonas spp., Chronobacte example, transfection, transformation, phage, electropora rium spp., Sinorhizobium spp., Saccharopolyspora spp., tion, biolistics etc.). Agrobacterium spp. and Pantoea spp. The bacterial cell can 0078. When selectable markers are used the number of be a Gram-negative cell Such as an E. coli, or a Gram-positive genomic loci targeted for combinatorial mutations can be cell such as a species of Bacillus. In other embodiments, the either 1:1 or 1:greater than 1 (marker:locus/foci). That is, a cell is a fungal cell such as a yeast cell, e.g., Saccharomyces selection marker may be tied to the targeting of a single site or spp., Schizosaccharomyces spp., Pichia spp., Pafia spp., the same marker may be tied to several targeted sites. When Kluyveromyces spp., Candida spp., Talaromyces spp., Bret used in a 1:1 manner, the selection ensures that the locus of tanomyces spp., Pachysolen spp., Debaryomyces spp., Yar interest has been modified. When used as 1:greater than 1 the rowia spp., and industrial polyploid yeast strains. Preferably marker ensures that at least one of the targeted loci have been the yeast strain is a S. cerevisiae strain or a Yarrowia spp. modified. Multiple recovery cycles for the markers will lead strain. Other examples of fungi include Aspergillus spp., Pen to an accumulation of Scars on the genome (e.g., loXP, FRT, nicilium spp., Fusarium spp., Rhizopus spp., Acremonium etc. sites) which may lead to genomic instability, thus spp., Neurospora spp., Sordaria spp., Magnaporifthe spp., decreasing the overall efficiency of the approach(es) due to Allomyces spp., Ustilago spp., Botrytis spp., and Tricho decreased viability in the population. derma spp. In other embodiments, the cell is an algal cell or a 0079 Another method of selection includes the use of a plant cell (e.g., A. thaliana, C. reinhardtii, Arthrospira, P site-specific nuclease (such as CRIPSR/Cas9 or a TALEN) tricomutum, T. Suecica, P. carterae, P tricomutum, Chlorella programmed to recognize the wildtype sequence of the Acti spp., Such as Chlorella vulgaris). Target cells can include nomycete spp genomic region targeted for diversification by transgenic and recombinant cell lines. In addition, heterolo the cassette conferring the homologous sequence as gous cell lines can be used, such as Chinese Hamster Ovary described herein. When coupled, e.g. in the same vector, to an cells (CHO). individual locus targeted by the cassette, this approach can 0083. In some embodiments the cell is a bacterial cell, result in a Scarless method for selecting recombinants and Such as Bacillus spp., Actinomycetes spp Escherichia spp., obviates the need for a selectable marker. In this case, recom Streptomyces spp., Zymomas spp., Acetobacter spp., Citro bination with the homologous target region mutated at the bacter spp., Synechocystis spp., Rhizobium spp., Clostridium wild-type locus targeted by the site-specific nuclease, is the spp., Corynebacterium spp., Streptococcus spp., Xanthomo only way to escape repeated cutting by the nuclease. In other nas spp., Lactobacillus spp., Lactococcus spp., Bacillus spp., words, recombination with the mutated sequence frees the Alcaligenes spp., Pseudomonas spp., Aeromonas spp., Azo organism from the genomic instability caused by the site tobacter spp., Comamonas spp., Mycobacterium spp., specific nuclease. Rhodococcus spp., Gluconobacter spp., Ralstonia spp., 0080. In some embodiments, the endogenous exonuclease Acidithiobacillus spp., Microlunatus spp., Geobacter spp., system(s), e.g. Rec), SbcCD, of the host Actinomycete spp. Geobacillus spp., Arthrobacter spp., Flavobacterium spp., are disrupted. Serratia spp., Saccharopolyspora spp., Thermus spp., 0081. In some embodiments, conjugation is used to trans Stenotrophomonas spp., Chromobacterium spp., Sinorhizo fer the mutated vector or plasmid from a MAGE-competent bium spp., Saccharopolyspora spp., Agrobacterium spp. and organism, e.g., Escherichia coli, to the host cell. For example Pantoea spp. The bacterial cell can be a Gram-negative cell the conjugation may employ the oriT system described as Such as an Escherichia coli (E. coli) cell, or a Gram-positive above to transform Streptomyces. In some embodiments, the cell such as a species of Bacillus. In other embodiments, the plasmid or vector system encodes the T-DNA or analogous cell is a fungal cell Such as a yeast cell, e.g., Saccharomyces system, to enable transfer of the mutated plasmid or vector spp., Schizosaccharomyces spp., Pichia spp., Pafia spp., DNA to plant cells with Agrobacterium (e.g., Agrobacterium Kluyveromyces spp., Candida spp., Talaromyces spp., Bret tumefaciens), as anyone skilled in the art will recognize, for tanomyces spp., Pachysolen spp., Debaryomyces spp., Yar the purpose of genetic engineering of plant cells. rowia spp., and industrial polyploid yeast strains. Preferably 0082. These systems thereby expand the engineering the yeast strain is a S. cerevisiae strain or a Yarrowia spp. approaches to essentially any host cell. For example, host strain. Other examples of fungi include Aspergillus spp., Pen cells can include eukaryotic and/or prokaryotic cells, includ nicilium spp., Fusarium spp., Rhizopus spp., Acremonium ing bacterial, yeast, algal, plant, insect, and/or non-human spp., Neurospora spp., Sordaria spp., Magnaporthe spp., mammalian cells, or immortal cell lines. For example, the Allomyces spp., Ustilago spp., Botrytis spp., and Tricho host cell may be Escherichia coli, Saccharomyces cerevisiae, derma spp. In other embodiments, the cell is an algal cell or a Pichia pastoris, Saccharomyces castelli, Kluyveromyces lac plant cell (e.g., A. thaliana, C. reinhardtii, Arthrospira, P tis, Pichia stipitis, Schizosaccharomyces pombe, Chlamy tricomutum, T. Suecica, P. carterae, P tricomutum, Chlorella US 2016/01 86168 A1 Jun. 30, 2016 spp., Such as Chlorella vulgaris). Target cells can include glucose-6-phosphate, fructose-6-phosphate, fructose-1,6- transgenic and recombinant cell lines. In addition, heterolo bisphosphate, 3-phosphoglyceraldehyde, dihydroxyacetone gous cell lines can be used, such as Chinese Hamster Ovary phosphate, glycerol. 1,3-bisphosphoglycerate, 3-phospho cells (CHO). Host cells may be unicellular host cells or mul glycerate, 2-phospho-glycerate, phosphoenolpyruvate, and ticellular host cells. pyruvate. In these embodiments, the increase flux may Sup 0084. In some embodiments, the cell suitable for use in port production of desired chemicals through one or more and/or with the compositions and methods described herein is recombinantly expressed genes or endogenous secondary an Actinomycetes spp. cell. Actinomycetes are a heteroge pathways. In some embodiments, increased flux Supports an neous collection of bacteria that form branching filaments increase in production of one or more amino acids (including which include, for example, Actinomyces, Actinomadura, aromatic amino acids and unnatural amino acids), fatty acids, Nocardia, Streptomyces and related genera. In some embodi carboxylic acids, nucleotides or nucleotide derivatives, and ments, Actinomyces comprise Streptomyces. In some polysaccharides. embodiments, the Actinomycetes spp. cell is a Streptomyces I0089. In some embodiments, the genomic engineering cell, (e.g. S. coelicolor). Streptomyces include, by way of methods alter carbon flux to increase or decrease the level of non-limiting example, S. noursei, S. nodosus, S. natalensis, S. one or more tricarboxylic acid cycle or glyoxylate pathway venezuelae, S. roseosporus, S. fradiae, S. lincolnensis, S. products or intermediates, such as citrate, cis-aconitate, isoci alboniger; S. griseus, S. rimosus, S. aureofaciens, S. cla trate, oxaloSuccinate, C.-ketoglutarate. Succinyl-CoA, Succi vuligerus, S. avermitilis, S. platensis, S. verticillus, S. hygro nate, fumarate, L-malate, oxaloacetate, and glyoxylate. In scopicus, and S. viridochroneogenes. these embodiments, the increase flux may support production 0085. In some embodiments, the cell suitable for use in of desired chemicals through one or more recombinantly and/or with the compositions and methods described herein is expressed genes or endogenous secondary pathways. In some a Subtillus spp. cell. In some embodiments, the Bacillus spp. embodiments, increased flux Supports an increase in produc cell is selected from B. alcalophilus, B. alvei, B. amino tion of one or more amino acids (natural or unnatural), fatty vorans, B. amyloliquefaciens, B. aneurinolyticus, B. anthra acids, and carboxylic acids. cis, B. aquaemaris, B. atrophaeus, B. boroniphilus, B. brevis, 0090. In these or other embodiments, the genomic engi B. Caldolyticus, B. centrosporus, B. cereus, B. circulans, B. neering methods alter carbon flux to increase or decrease the coagulans, B. firmus, B. flavothermus, B. fusiformis, B. gall level of one or more Entner-Doudoroff intermediates or prod iciensis, B. globigii, B. infernus, B. larvae, B. laterosporus, B. ucts, such as 6-phospho-gluconate or 2-keto-3-deoxy-6- lentus, B. licheniformis, B. megaterium, B. mesentericus, B. phospho-gluconate (KDPG). mucilaginosus, B. mycoides, B. natto, B. pantothenticus, B. 0091. In these or other embodiments, the genomic engi polymyxa, B. pseudoanthracis, B. pumilus, B. Schlegelii, B. neering methods alter carbon flux to increase or decrease the sphaericus, B. sporothermodurans, B. Stearothermophilus, B. level of one or more pentose phosphate pathway intermedi subtilis, B. thermoglucosidasius, B. thuringiensis, B. vulga ates or products, such as ribulose, Xylulose, fructose, and/or tis, and B. Weihenstephanensis. ribose, or phosphorylated form thereof. I0086. In various embodiments, the present invention per 0092. In these or other embodiments, the genomic engi tains to probiotics. For example, the present multiplex neering methods alter carbon flux to increase or decrease the genome engineering techniques are used to alter probiotic level of one or more phosphoketolase pathway intermediates cells to, for example, increase the functionality of the probi or products, such as 6-phosphoglucolactone, pyruvic acid, otic cells (e.g. increase digestion, synthesize various vitamins lactic acid, acetyl phosphate, acetyl CoA, acetylaldehyde, or amino acids, decrease pathogens, etc.). Accordingly, vari and/or ethanol. ous probiotic species are a cell of the present invention. For 0093. In these or other embodiments, the genomic engi example, the cell may be E. coli Nissle 1917. By way of neering methods alter carbon flux to increase or decrease the further illustration, the cell is a lactobacillus (e.g. acidophi level of one or more non-mevolonate pathway products or lus, Lactobacillus brevis, L. bulgaricus, L. plantarum, L. intermediates, such as Isopentenyl diphosphate (IPP), dim rhamnosus, Rhamnosus L. fermentum, L. Caucasicus, L. hel ethylallyl pyrophosphate DMAPP 1-deoxy-D-xylulose veticus, L. lactis, L. reuteri and L. casei) or a bifidobacteria 5-phosphate (DXP), 2-C-methyl-D-erythritol 4-phosphate, (Bifidobacterium bifidum, B. infantis) Streptococcus thermo 4-diphosphocytidyl-2-C-methylerythritol, 4-diphosphocyti philes, and Enterococcus faecium. dyl-2C-methylerythritol 2-phosphate, 2-C-methyl-D-eryth 0087. In various embodiments, one or more of these pro ritol 2.4-cyclodiphosphate. These intermediates can be used cesses are used to target regions of the host, including both to Support production ofisoprene or terpenoid compounds in endogenous and recombinant genes, for diversity. In some host cells. embodiments, the genomic engineering methods alter or 0094. In these or other embodiments, the genomic engi diversify the suitable feedstock for a host cell. For example, neering methods alter carbon flux to increase or decrease the the process may enhance the usage offeedstock selected from level of one or more meVolonate pathway products or inter industrial or municipal waste, syngas, methane, as well as mediates. Such as HMG-CoA, mevalonate, 5-phosphomeva cellulosic or lignocellulosic feedstocks, such as Sugar cane lonate, 5-pyrophosphomevalonate, 3-isopentyl pyrophos bagasse, wheat Straw, corn Stover, or other. For example, the phate, and dimethylallyl pyrophosphate. These intermediates feedstock may be processed from cardboard, paper, yard can be used to Support production of isoprene or terpenoid waste and/or other agricultural waste. In some embodiments, compounds in host cells. the recombineered strain enhances the availability of five 0095. In some embodiments, the method targets one or and/or six carbon Sugars that are available for metabolism. more genes of central metabolism to direct carbon flux to 0088. In some embodiments, the genomic engineering desired carbon skeleton. For example, the method may target methods alter carbon flux to increase or decrease the level of one or more genes (e.g., from 1 to 30 genes, or from 1 to 20 one or more glycolysis intermediates or products, such as genes, or from 1 to 10 genes, including 1, 2, 3, 4, 5, 6, 7, or 8 US 2016/01 86168 A1 Jun. 30, 2016 genes) of microbial central metabolic pathways, including Doudoroff, pentose phosphate, phosphoketolase pathway, glycolysis, tricarboxylic acid cycle, Embden-Meyerhof-Par and glyoxylate pathway (or others described herein). The nas, Entner-Doudoroff, pentose phosphate, phosphoketolase engineering round is conducted by varying at least one Sub pathway, and glyoxylate shunt. In some embodiments, the sequence of each enzyme or related genomic target, such as strain producing the desired chemical or product has from 1 to the ribosomal binding sequence, so as to produce an engi 10 genes (e.g., 1-5 genes, or 1-3 genes, or 5-10 genes) targeted neered library of mutants with decreases and increases in by the processes described herein selected from: hexokinase, expression of each enzyme, change in cellular localization isomerase, phosphofructokinase, fructose-1,6-bisphosphate with or without respect to other pathway components, func aldolase, triosephosphate isomerase, triosephosphate dehy tional characteristics of one or more enzymes, as well as drogenase, phosphoglycerate kinase, mutase, enolase, pyru additional endogenous components that may affect cellular vate kinase, transketolase, transaldolase, ribulose phosphate characteristics affecting the performance of one or more path epimerase, phosphatase, lactonase, glucose 6-phosphate way components (e.g., pH, import/export, degradation rates, dehydrogenase, gluconate dehydrogenase, pentose phos etc.) and various combinations thereof. phate isomerase, xylulose epimerase, KDPG aldolase, PGA 0101. In various embodiments the invention provides kinase, citrate synthase, aconitase, isocitrate dehydrogenase, methods to employ combinatorial in vivo Screening of syn C.-ketoglutarate dehydrogenase, Succinate thiokinase, Succi thetic scaffolds to a set of enzymes involved in production of nate dehydrogenase, fumarase, malate dehydrogenase, isoci a desired target molecule (John E. Dueber, Gabriel C Wu, G trate lyase, malate synthase, PEP carboxykinase, and PEP Reza Malmirchegini, Tae Seok Moon, Christopher J Petzold, synthetase. AdeetiV Ullal, Kristala LJ Prather & Jay DKeasling. (2009) 0096. In some embodiments, the compound is a productor Synthetic protein scaffolds provide modular control over intermediate of microbial metabolism, or a derivative thereof metabolic flux. Nature Biotechnology 27 (8): 753-759. Whi produced by the expression of one or more recombinant taker, W. R., & Dueber, J. E. (2011). Metabolic Pathway Flux genes. The compound may be a product of one or more Enhancement by Synthetic Protein Scaffolding. Synthetic recombinant genes to synthesize and enhance production of a Biology, Part A, 1, 447-478, and International Patent Publi compound not inherently produced, or not produced at sig cation No. WO/2009/108774, the contents of which are incor nificant levels by the host cell. These compounds include porated by reference in their entirety). Having then generated compounds having C2-C6 carbon skeletons that are likely to any number of strains with mutations in these various aspects, rely largely on primary metabolism. these cells are subjected to a selection or screen for the pro 0097. In some embodiments, the compound has a C2 car duction of a desired compound or intermediate. Any suitable bon skeleton, which may be include one or more groups chemical, analytical, biochemical, biophysical, microbio selected from hydroxyl, amino, or Oxy. Exemplary com logic, phenotypic screen common in the art may be applied to pounds include ethylene, ethanol, ethene, ethane, and acetate. identify the improved strain. Non-limiting examples of In some embodiments, the compound is a C3 carbon skeleton, screening methods include chromatographic analysis, spec which may include one or more groups selected from troscopic analysis, extraction followed by an analytical chro hydroxyl, amino, or Oxy. Exemplary compounds include matographic step, chemical chromogenic assay, flow cyto pyruvate, methacrylic acid, acrylate, propanoic acid, hydrox metric analysis and Sorting, enzymatic activity assay, Zone of ypropanoic acid, propylene, propanol, isopropanol, propane, inhibition assay, auxotrophic reporter strain growth assay, and propene. In some embodiments, the compound is a C4 etc. By then determining the incorporated sequences that carbon skeleton, which may include one or more groups gave rise to the increased production, further rounds of tar selected from hydroxyl, amino, or Oxy. Exemplary com geted genomic engineering may be conducted on the identi pounds include butanol, isobutanol, butadiene, butanediol. fied genes. butanone, butyric acid, butyrolactone, butanal, putrescine, 0102 Alternatively or in combination, a sensor strategy fumarate, and malate. In some embodiments, the compound may be coupled to a selectable marker or system to identify is a C5 carbon skeleton which may include one or more improved strains. A competitive advantage. Such as improved groups selected from hydroxyl, amino, or Oxy. Exemplary growth, can be induced by a system engineered to respond to compounds include levulinic acid, pentanoic acid. In some the phenotypic improvement being sought, such as higher embodiments, the compound is a C6 carbon skeleton, which production of a metabolite. See, e.g., Berteis F. Merker H. may include one or more groups selected from hydroxyl, Kost C (2012) Design and Characterization of Auxotrophy amino, or oxy. Exemplary compounds include caproic acid, Based Amino Acid Biosensors. PLoS ONE 7(7): e41349. For cyclohexanone, or adipate. instance, a chemical binding transcription factor can be used 0098. The invention as described can employ tools that are to drive expression, via its cognate promoter, of a selectable standard in molecular biology. marker, such as TolC. Expression of the selectable marker 0099. In these or other embodiments, from one to about may be modulated through means Such as transcription factor 100 (or more), or from one to about fifty, or from one to about recruitment or mRNA processing (riboswitch) as long as the twenty (e.g., from one to ten or from one to five genes) of expression is regulated by the improved phenotype. Non secondary biosynthetic pathways (such as amino acid biosyn limiting examples of sensors include LacI for IPTG or a thetic pathways) are also targeted for genetic diversity and riboswitch for riboflavin. screened for desired phenotype. 0103) Additionally, the screening techniques may be used 0100. In some embodiments, genetic components that singly or in combination. In one instance, a sensor-selector enhance the production of a desired compound are selected in screen may be applied to identify a series of high producing multiple repeating stages. First, an engineering round is con strains which are then interrogated for best performers by use ducted to target all genes of one or more pathways. Such as of a quantitative chromatographic assay. one or more (or three, four, five, or more) of glycolysis, 0104. In some embodiments, the host cell or strain is engi tricarboxylic acid cycle, Embden-Meyerhof-Parnas, Entner neered to enhance the expression or activity of one or more US 2016/01 86168 A1 Jun. 30, 2016

recombinant genes such that genes are regulated and opti mide, GM1, GM2, GM3, Prostanoic acid, Prostaglandin A1, mized for product development. For example, the target Prostaglandin A2, Prostaglandin B1, Prostaglandin B2, Pros recombinant enzyme may be one or more of an oxidoreduc taglandin C1, Prostaglandin C2, Prostaglandin D1, Prostag tase, transferase, hydrolase, lyase, isomerase, or ligase spe landin D2, Prostaglandin E1, Prostaglandin E2. Prostaglan cific for the desired substrate, and which may be a product of din E3, Prostaglandin F1alpha, Prostaglardin F2alpha, a core metabolic pathway as described, or an endogenous Prostaglandin F2beta, Prostaglandin F3alpha, Prostaglandin biosynthetic pathway. In some embodiments, at least one G2, Prostaglandin H2, Prostaglandin I2, Prostaglandin J2, enzyme is an endogenous or heterologous cytochrome P450 Leukotriene A4, Leukotriene B4, Leukotriene C4, Leukot oxidase enzyme, which may be fused in some embodiments riene D4, Leukotriene E4, Leukotriene F4, 5-HPETE, to its reductase partner. Thromboxane A2. Thromboxane B2, 11-Dehydro-throm 0105. In other aspects, the invention provides engineered boxane B2, D-Glyceraldehyde, L-Glyceraldehyde, D-Eryth cells made through processes described herein, and provides rose (Ery), D-Threose (Tho), D-Arabinose (Ara), L-Arabi methods of producing these products through fermentation of nose, D-Xylose (Xyl), L-Xylose, D-Lyxose (LyX), L-Lyxose, the engineered cells. For example, the methods and cells may, D-Ribose (Rib), D-Glucose (Glc), D-Galactose (Gal), L-Ga in various embodiments, produce a biofuel Such as methanol, lactose, D-Mannose (Man), D-Allose (All), D-Altrose (Alt), ethanol, propanol, butanol, or isobutanol, or a compound D-Gulose (Gul), L-Gulose, D-Idose (Ido), D-Talose (Tal), having a C2 to C6 carbon skeleton (for example) ethylene, 3.6-Anhydrogalactose, 3.6-Anhydroglucose, Dihydroxyac acetate, methacrylic acid, acrylate, lactic acid, isoprene, pro etone, D-Erythrulose, L-Erythrulose, D-Ribulose, L-Ribu panoic acid, hydroxypropanoic acid, propylene, propane, lose, D-Xylulose (Xul), L-Xylulose, D-Fructose (Fru); Fruit propene, butadiene, butanediol, butanone, butyric acid, buty sugar, L-Fructose, D-Sorbose (Sor), L-Sorbose, D-Tagatose rolactone, butanal, putrescine, fumarate, malate, levulinic (Tag), D-Psicose, Sedoheptulose (Sed), Coriose, Deoxyri acid, pentanoic acid, caproic acid, cyclohexanone, or adipate. bose, D-Fucose (Fuc), L-Fucose, D-Rhamnose (Rha), In some embodiments, the compound is a fatty acid, amino L-Rhamnose, 2-Deoxy-D-glucose, D-Quinovose (Qui), acid, lipopeptide, antibiotic, nucleotide or nucleotide deriva 2-Deoxy-D-galactose, Abequose, D-Glucosamine (GlcN), tive, or terpenoid. Other potential chemical products are dis D-Galactosamine (GalN), D-Mannosamine (ManN), D-Fu closed elsewhere herein. cosamine (FucN), D-Quinovosamine (QuiN), Neuraminic 0106. In various embodiments, the present invention pro acid (Neu), Muramic acid (Mur), N-Acetyl-D-glucosamine vides for, interalia, methods of making a desired compound (GlcNAc), N-Acetyl-D-galactosamine (GalNAc), N-Acetyl and methods of making a cell capable of producing a desired D-mannosamine (ManNAc), N-Acetyl-D-fucosamine (Fuc compound. In various embodiments, the present invention NAc), N-Acetyl-D-quinovosamine (QuiNAc), N-Acetyl provides for, interalia, methods of targeting synthetic path neuraminic acid (Neu5Ac), N-Acetylmuramic acid ways of the desired compound genes and/or secondary path (MurNAc), O-Acetylneuraminic acid, N-Glycoloyl-neu ways that control effect flux through the synthetic pathways raminate, D-Fructuronic acid, D-Tagaturonic acid, D-Glucu for allelic replacement. ronic acid (GlcA), D-Galacturonic acid (GalA), D-Mannu 0107. In some embodiments, the desired compound is as ronic acid (ManA), L-Iduronic acid (IdoA), L-Guluronic listed below. In some embodiments, the desired compound acid, D-Gluconic acid, D-Glucosaminic acid, 2-Keto-D-glu includes Formate; Methanoate, Acetate; Ethanoate, Propi conic acid, 3-Deoxy-D-manno-octulosonic acid, Sucrose; onate; Propanoate, Butyrate; Butanoate, Valerate; Pen Cane Sugar, Lactose; Milk Sugar, Maltose; Malt Sugar, Iso tanoate, Capronate, Hexanoate, Enanthate; Heptanoate, maltose, Trehalose, Cellobiose, Gentiobiose, Kojibiose, Caprylate; Octanoate, Oxalate, Malonate. Succinate, Glut Laminaribiose, Maltulose, Mannobiose, Melibiose, Melibiu arate, Adipate, Pimelate, Suberic acid, Citrate, Isocitrate, cis lose, Nigerose, Palatinose, Rutinose, Scillabiose, Turanose, Aconitate, trans-Aconitate, Pyruvate: 2-Oxopropanoate, Vicianose, Xylobiose, Adenine (Ade), Guanine (Gua), Uracil 2-Oxobutanoate, 2-OXopentanoic acid, 2-Oxohexanoic acid, (Ura), Thymine (Thy), Cytosine (Cyt), Adenosine (A), Gua Oxaloacetate: 2-OXobutanedioic acid, 2-Oxoglutarate, nosine (G), Uridine (U), Cytidine (C), Deoxyadenosine (dA), 2-Oxoadipate, 2-Oxopimelate, 2-Oxoisovalerate, 4-Methyl Deoxyguanosine (dG), Deoxyuridine (dU), Deoxythymidine 2-oxopentanoate, (S)-3-Methyl-2-oxopentanoic acid, (dT), Deoxycytidine (dC), AMPADPATP, GMP, GDP, GTP, Butyric acid (4:0). Caproic acid (6:0), Caprylic acid (8:0). UMP, UDP, UTP, CMP, CDP, CTP, dAMP, dADP, dATP, Capric acid (10:0), Lauric acid (12:0), Myristic acid (14:0). dGMP, dGDP, dGTP, dUMP, dUDP, dUTP, dTMP, dTDP. Palmitic acid (16:0), Stearic acid (18:0), Arachidic acid (20: dTTP, dCMP, dCDP, dCTP 3',5'-Cyclic AMP. 3',5'-Cyclic O), Behenic acid (22:0), Lignoceric acid (24:0), Oleic acid GMP. 3',5'-Cyclic IMP. 3',5'-Cyclic dAMP, 3',5'-Cyclic (18:1:9), Elaidic acid (18:1:9), Icosenoic acid (20:1:11), Eru dGMP, 3,5'-Cyclic CMP, 2,3'-Cyclic AMP, 2,3'-Cyclic GMP, cic acid (22:1:13), Nervonic acid (24:1:15), Linoleic acid 2',3'-Cyclic CMP. 2',3'-Cyclic UMP, Glycine (Gly), Alanine (18:2:9,12), Icosadienoic acid (20:2:11, 14), Docosadienoic (Ala), Valine (Val), Leucine (Leu), Isoleucine (lie), Aspartic acid (22:2:13,16), gamma-Linolenic acid (18:3:6.9.12), acid (Asp), Asparagine (ASn), Glutamic acid (Glu), alpha-Linolenic acid (18:3:9,12,15), Arachidonic acid (20:4: Glutamine (Gin), Serine (Ser), Threonine (Thr), Methionine 5,8,11,14), Eicosapentaenoic acid (20:55,8,11,14,17), (Met). Cysteine (CyS), Lysine (LyS), Arginine (Arg). Histi Docosahexaenoic acid (22:6:4,7,10,13,16,19), Glycerol, dine (His), Proline (Pro), Phenylalanine (Phe), Tyrosine 1-Monoacylglycerol, 2-Monoacylglycerol. 1,2-Diacylglyc (Tyr), Tryptophan (Trp), Selenocysteine (Sec), Pyrrolysine erol, 1,3-Diacylglycerol, Triacylglycerol, Phosphatidic acid, (Pyl), L-Ornithine, L-Homocysteine, L-Homoserine, L-Cit Phosphatidylethanolamine, Phosphatidylcholine; Lecithin, rulline, 3-Sulfino-L-alanine, L-Argininosuccinate, 3,4-Dihy Phosphatidylserine, Phosphatidylinositol, 2-Lysolecithin, droxy-L-phenylalanine, 3-Iodo-L-tyrosine, 3,5-Diiodo-L-ty Plasmenylethanolamine, Plasmenylcholine, Phosphatidylg rosine, Triiodothyronine, L-Thyroxine, beta-Alanine, lycerol, Diphosphatidylglycerol; Cardiolipin, Sphingomy gamma-Aminobutyric acid, 3-Aminoisobutyric acid, D-Ala elin, Glucosylceramide, Galactosylceramide, Lactosylcera nine, D-Valine, D-Leucine, D-Isoleucine, D-Aspartic acid, US 2016/01 86168 A1 Jun. 30, 2016

D-Asparagine, D-Glutamic acid, D-Glutamine, D-Serine, mone, Chorionic gonadotropin, Calcitonin, Parathyroid hor D-Threonine, D-Methionine, D-Cysteine, D-Lysine, D-Argi mone, Atrial natriuretic peptide, Brain natriuretic peptide, nine, D-Histidine, D-Proline, D-Phenylalanine, D-Tyrosine, C-Type natriuretic peptide, Endothelin-1, Endothelin-2, D-Tryptophan, Pidolic acid, Hydroxyproline, Cystine, Endothelin-3, Glucagon, Insulin, Amylin, Peptide YY. Gas N-Formylmethionine, Ethanolamine, Cysteamine, Amino trin-14, Gastrin-17, Gastrin-34, Cholecystokinin-8, Chole propanol, gamma-Aminobutyric acid (GABA). Histamine, cystokinin-33, Motilin, Secretin, Thymosin alpha-1, Thy Dopamine, Serotonin, Putrescine, S-Adenosylmethioni mosin beta-4, Thymosin beta-10. Insulin-like growth factor I, namine, Tyramine, Phenethylamine, Retinal (Vitamin A), Insulin-like growth factor II, Erythropoietin, Angiotensin I. Angiotensin II, Angiotensin III, Angiotensin IV, Bradykinin, Ergocalciferol (Vitamin D2), Cholecalciferol (Vitamin D3), Leptin, Adiponectin, Resistin, 7alpha-Hydroxytestosterone, alpha-Tocopherol (Vitamin E), Phylloquinone (Vitamin K1), Dehydroepiandrosterone sulfate, 19-Hydroxytestosterone, Menaquinone (Vitamin K2), Menadione (Vitamin K3). Thia Estrone 3-sulfate, 16alpha-Hydroxyestrone, 17alpha-Hy mine (Vitamin B1), Riboflavin (Vitamin B2), Nicotinic acid droxyprogesterone, 17alpha-Hydroxypregnenolone, (Vitamin B3), Nicotinamide (Vitamin B3), Pantothenic acid 11-Deoxycortisol, Tetrahydrocortisone, 21-Deoxycortisol, (Vitamin B5), Pyridoxal (Vitamin B6), Pyridoxine (Vitamin 18-Hydroxycorticosterone, 11-Dehydrocorticosterone, Cal B6), Pyridoxamine (Vitamin B6), Biotin (Vitamin B7), Folic acid (Vitamin B9), Cobalamin(III) (Vitamin B12), Ascorbic citriol (Vitamin D), Melatonin, Thyroxine, Adrenaline, Nora acid (Vitamin C), SAM, Coenzyme B, Coenzyme F430. drenaline, Acetylcholine, Glycine, Aspartate, Glutamate, Coenzyme M. Coenzyme Q10, Glutathione, Methanofuran, GABA, Dopa, Epinephrine; Adrenaline, Norepinephrine; PAPS, Tetrahydrobiopterin, 5,6,7,8-Tetrahydromethanop Noradrenaline, Penicillin G, Ampicillin, Cephalosporin C, Cephamycin C, Cefazolin, Ceftriaxone, Clavulanic acid, terin, Heme A, Heme C, Heme O, Lipoate, Molybdopterin, Thienamycin, Imipenem, Nocardicin A, Aztreonam, Strepto PQQ. Gonane, 5alpha-Gonane, 5beta-Gonane, Estrane, mycin, Spectinomycin, Kanamycin, Gentamicin C, Neomy Allylestrenol, Estradiol-17alpha, Estradiol-17beta, Estriol, cin B. Butirosin A, Erythromycin, Oleandomycin, Tylosin, Estrone, Epimestrol, Equilin, Equilenin, 5beta-Estrane-3al Candicidin D, Geldanamycin, Rifamycin W. Rifampicin, Tet pha,17beta-diol, Estramustine, 2-Hydroxyestradiol, 6beta racycline, Adriamycin, Actinorhodine, Tetranactin, Mon Hydroxyestradiol-17beta, 2-Methoxyestradiol-17beta, ensin, Griseofulvin, Vancomycin, Teicoplanin A2-2, Bleo Methyltrienolone, Mifepristone, Nandrolone, Trenbolone, mycin B2, Bacitracin A, Valinomycin, Polymyxin B, 5alpha-Androstane, Adrenosterone, Androsterone, 5beta Actinomycin D. Nalidixic acid, Norfloxacin, Nojirimycin, Androstane-3,17-dione, Androstanediol, 3-Androstanol, Flavomycin, Cycloserine, Polyoxin B, Cycloheximide, Androstenediol, Androstenedione, 4-Androstenediol, Dehy droepiandrosterone, Dihydrotestosterone, Etiocholanolone, Fusidic acid, Chloramphenicol, Novobiocin, Fosfomycin, Oxandrolone, Oxymetholone, Stanozolol, Testolactone, Tes Mitomycin, and 2-Oxazolidinone. tosterone, Pregnane, Aldosterone, Betamethasone, Beclom 0108. In some embodiments, the desired compound is as ethasone, Corticosterone, Cortisol, Cortisone, Danazol, Dex listed below. In some embodiments, the desired compound is amethasone, 11-Deoxycorticosterone, Ethisterone, as listed below and obtainable from an Archaea cell. Desired Fluocidnolone, Fluocinonide, Fluorometholone 17-acetate, compounds include Acetolactate synthase, Adenosylcobina Megestrol, Norethindrone, Norethynodrel, Norgestrel, Pred mide-GDP ribazoletransferase, ADP-specific glucokinase, nisolone, Prednisone, Pregnenolone, Progesterone, Spirono ADP-specific phosphofructokinase, Aminoimidazolase, lactone, Cardanolide, Cymarin, Gitoxin, Neriifolin, Digi 2-Amino-(1,2,3-trihydroxypropyl)-4-(1H)-pteridinone; (1S, toxin, Digoxin, Ouabain, 5alpha-Cholane, Apocholic acid, 2R)-form, 3'-O-B-D-Glucopyranoside, Anthranilate phos Chenodeoxycholate, 3-Oxo-5beta-cholanate, Cholic acid, phoribosyltransferase, Archaeol, Archaeol: 1-O-O-D-Ga 5beta-Cholanic acid, Dehydrocholic acid, Deoxycholic acid, lactofuranosyl-(1->3)-B-D-galactopyranosyl-(1->6)-C-D- Glycocholate, Hyodeoxycholate, Lithocholic acid, Tauro mannopyranosyl-(1->2)-O-D-galactopyranoside, Archaeol; cholate, Ursodiol, Bufanolide, Bufadienolide, Bufalin, Bufo 1-O-C-D-Galactofuranosyl-(1->3)-3-O-sulfo-f-D-galac talin, Cinobufagin, Cinobufotalin, Gamabufogenin, Proscil topyranosyl-(1->6)-C-D-mannopyranosyl-(1->2)-O-D-ga laridin, Scillarenin, Scilliroside, Telocinobufagin, lactopyranoside, Archaeol; 1-O-B-D-Galactopyranosyl-(1- Cholestane, Allocholesterol, Cholesterol, 7-Dehydrocholes >6)-C-D-glucopyranosyl-(1->2)-C-D-galactopyranoside. terol. DesmoSterol, Ecdysone, Spirostan, Digitogenin, Dios Archaeol: 1-O-B-D-Galactopyranosyl-(1->6)-C-D-man genin, Gitogenin, Sarsasapogenin, Smilagenin, Tigogenin, nopyranosyl-(1->2)-O-D-glucopyranoside, Archaeol; 1-O Furostan, Nuatigenin, Pseudoligogenin, Pseudosarsasapoge B-D-Glucopyranoside, Archaeol: 1-O-B-D-Glucopyrano nin, PseudoSmilagenin, Ergostane, Ergostanol, alpha-Ergos syl-(1->6)-C-D-mannopyranosyl-(1->2)-O-D-glucopyrano tenol, Ergosterol, Lumisterol. 5alpha-Campestane, Brassino side, Archaeol: 1-O-3-O-Sulfo-f-D-galactopyranosyl-(1- lide, Campestanol, Campesterol, StigmaStane, Fucosterol, >6)-C-D-mannopyranosyl-(1->2)-O-D-glucopyranoside. Stigmastanol, Stigmasterol, 5alpha-Poriferastane, Poriferas Archaeol: 1-O-2-Sulfo-O-D-mannopyranosyl-(1->2)-O-D- terol, gamma-Sitosterol, Gorgostane, Acanthasterol, Gorgos glucopyranoside. Argimicin B, Argimicin B; Amide, terol, Sarcoaldesterol A, Prolactin-releasing peptide-31, Pro Argimicin B; 4'-Deoxy, amide, Aromatic amino acid tran lactin-releasing peptide-20, Thyrotropin-releasing hormone, saminases: Aromatic amino acid transaminase, AstaXanthin; Gonadotropin-releasing hormone I, Gonadotropin-releasing (3S,3'S)-form, Di-O-O-L-rhamnopyranoside, Bacterior hormone II, Growth hormone-releasing hormone (1-29), hodopsin, Bacterioruberin; 3"-Deoxy. 2",3'-didehydro, Somatostatin-14, Somatostatin-28, Corticotropin releasing 3-Benzyl-6-(2-methylpropyl)-1,2,4,5-tetrathiane, Bis-y- hormone, Gastrin-releasing peptide, Melanin-concentrating glutamylcystine reductase, 3.6-Bis(2-methylpropyl)-1,2,4,5- hormone, Ghrelin, Oxytocin, Arg-Vasopressin, Corticotro tetrathiane, 1.2-Bis-O-(3,7,11,15,19-pentamethyleicosyl) pin, alpha-Melanotropin, beta-Melanotropin, gamma-Mel glycerol; 3-O-(2-O-O-D-Glucopyranosyl-myo-inosit-1- anotropin, Growth hormone, Prolactin, Thyroid stimulating ylphosphate), 1.2-Bis-O-(3,7,11,15,19-pentamethyleicosyl) hormone, Luteinizing hormone, Follicle stimulating hor glycerol: 3-O-(myo-Inosit-1-ylphosphate), 1.2-Bis-O-(3.7, US 2016/01 86168 A1 Jun. 30, 2016

11, 15-tetramethyl-2,6,10-hexadecatrienyl)glycerol, Factor F430, Factor F430; Penta-Me ester, Formylmethano Caldarchaeol, Caldarchaeol; O-(2-Aminoethylphosphoryl), furan:tetrahydromethanopterin N-formyltransferase, 1,6-O- Caldarchaeol; O-(2-Aminoethylphosphoryl), O'-B-D-glu L-Fucosidase, B-D-Galactopyranosyl-(1->6)-C-D-man copyranosyl-(1->6-B-D-glucopyranoside, Caldarchaeol; nopyranosyl-(1->2)-D-glucose, Geranylgeranylglycerol O-C-D-Glucopyranosyl-(1->4)-B-D-galactopyranoside, phosphate geranylgeranyltransferase, Glionitrin A, Glioni Caldarchaeol; O-B-D-Glucopyranosyl-(1->6-B-D-glucopy trin B. Glucan 1,4-O-maltotriohydrolase, 4-O-Glucanotrans ranoside, Caldarchaeol; O-(2-Hydroxymethyl-2,3,4,5-tet ferase, 4-O-D-(1->4)-O-D-Glucano trehalose trehalohydro rahydroxy)cyclopentyl ether, Caldarchaeol; O-(1-D-myo lase, O-Glucosidase, Halocins, Halocins; Haloan C8, Inositylphosphoryl), Caldarchaeol; O-(1-D-myo Halocins; Halocin H1, Halocins; Halocin H4, Halocins; Inositylphosphoryl), O'-B-D-galactopyranoside, Halocin H6, Halocins; Halocin KPS1, Halocins; Halocin Caldarchaeol; O-(1-D-myo-Inositylphosphoryl), O'-O-D- Sech7a, 2-(15.9, 13.17.21-Hexamethyldocosyl)benzo 1.2-b: glucopyranosyl-(1->4)-3-D-galactopyranoside, Caldar 4,5-b'dithiophene-4,8-dione, 1,3,4,6-Hexanetetracarboxylic chaeol; O-(1-D-myo-Inositylphosphoryl), O'-B-D-glucopy acid, 1,3,4,6-Hexanetetracarboxylic acid; (3RS.4SR)-form, ranosyl-(1->6)-B-D-glucopyranoside. Caldarchaeol; Homoserine kinase, 3-Hydroxybutanoic acid; (R)-form, Tet O—(O-Serylphosphoryl), O'-B-D-glucopyranosyl-(1->6)- ramer, 3-32-1-(Hydroxymethyl)-2-(phytanyloxy)ethyl B-D-glucopyranoside, Caldariellaquinone, Calditol, Coen oxydiphytanyloxy-2-phytanyloxy-1-propanol. 2-(1H-In Zyme-B sulfoethylthiotransferase, Coenzyme F420, Cyano dol-3-ylmethyl)-1H-indole-3-acetic acid, 4-(3- 5-hydroxybenzimidazolylcobamide, Cyano-5- Indolylmethyl)-7-(2-methylpropyl)-1,2,3,5,6-pentathiepane, methylbenzimidazolylcobamide, dCTP deaminase, 14.22. 3-(3-Indolylmethyl)-5-(2-methylpropyl)-1,2,4-trithiolane, 26.29,33,50,58,62.65,69-Decamethyl-8,1144,47 Isocaldarchaeol, Lipoyl synthase, Methanofuran, Methano tetraoxaheptacyclo[68.2.1.12.5.118,21.134.37.138.41.154, furan b. Methanophosphagen, Methanopterin, Methenyltet 57 octaheptacontane-10.46-dimethanol, 14.22.26.29.33.50, rahydrofolate cyclohydrolase, Methylated-DNA-protein 58.62.65,69-Decamethyl-8,1144.47-tetraoxaheptacyclo68. cysteine S-methyltransferase, 15-Methyl-5-hexadecenoic 2.1.12.5.118,21.134.37.138.41.154.57 octaheptacontane acid; (E)-form, Methylhexathiepane, 3-Methyl-8-(2-methyl 10.46-dimethanol: 10'-O-(2-Hydroxymethyl-2,3,4,5- propyl)-1,2,4,5-tetrathiane, (2-Methylpropyl)heptathiocane, tetrahydroxycyclopentyl), 2-Dehydro-3- (2-Methylpropyl)hexathiepane, (2-Methylpropyl)pen deoxygluconokinase, 2-Deoxy-arabino-hexuronic acid; tathiane, S-Methyl-5'-thioadenosine phosphorylase, MJ D-form, 4,7-Dialkyl-1,2,3,5,6-pentathiepanes, 4,7-Dialkyl 0684, NAD(+) kinase, Nicotinamide nucleotide adenylyl 1,2,3,5,6-pentathiepanes: 4-Benzyl-7-(2-methylpropyl)-1.2. transferase, Nicotinate phosphoribosyltransferase, 4-Nitro 3,5,6-pentathiepane, 4,7-Dialkyl-1,2,3,5,6-pentathiepanes; phenylphosphatase, 22.26.29.33.50.58,62.65,69-Nonam 4.7-Bis(2-methylpropyl)-1,2,3,5,6-pentathiepane, 4,7-Di ethyl-8,1144.47-tetraoxaoctacyclo68.2.1.12.5.114, 17.118, alkyl-1,2,3,5,6-pentathiepanes: 4-Isopropyl-7-(2-methylpro 21.134.37.138.41.154,57nonaheptacontane-10.46 pyl)-1,2,3,5,6-pentathiepane, 4,7-Dialkyl-1,2,3,5,6-pen dimethanol, 22.26.29,33,50,58,62.65,69-Nonamethyl-8,11, tathiepanes; 4-Methyl-7-(2-methylpropyl)-1,2,3,5,6- 44,47-tetraoxaoctacyclo68.2.1.12.5.114, 17.118.21.134.37. pentathiepane, 4.7-Dialkyl-1,2,3,5,6-pentathiepanes: 4-(2- 138.41.154,57nonaheptacontane-10.46-dimethanol; 10'-O- Methylpropyl-1,2,3,5,6-pentathiepane, 3,5-Dialkyl-1,2,4- (2-Hydroxymethyl-2,3,4,5-tetrahydroxycyclopentyl), 7,1 1, trithiolanes, 3.5-Dialkyl-1,2,4-trithiolanes; 3-Benzyl-5-(2- 15, 19.22.26.30,34-Octamethyl-1,4- methylpropyl)-1,2,4-trithiolane, 3,5-Dialkyl-1,2,4- dioxacyclohexatriacontane-2-methanol. 3,7,11,15, 18.22.26. trithiolanes; 3-Benzyl-5-methyl-1,2,4-trithiolane, 3.5- 30-Octamethyl-1,32-dotriacontanediol; (3R,7R,11S, 15R, Dialkyl-1,2,4-trithiolanes; 3.5-Bis(2-methylpropyl)-1,2,4- 18.R.22S.26R,30R)-form, 22,26,29,33,58,62,65,69 trithiolane, 3,5-Dialkyl-1,2,4-trithiolanes; 3-Ethyl-5-(2- Octamethyl-8, 11,44.47-tetraoxanonacyclo68.2.1.12.5.114, methylpropyl)-1,2,4-trithiolane, 3,5-Dialkyl-1,2,4- 17.118.21.134.37.138.41.150,53.154.57 octacontane-9,45 trithiolanes; 3-Ethyl-5-methyl-1,2,4-trithiolane, 3.5-Dialkyl dimethanol, 22.26.29.33,58,62.65,69-Octamethyl-8, 11.44, 1,2,4-trithiolanes; 3-Isopropyl-5-(2-methylpropyl)-1,2,4- 47-tetraoxanonacyclo[68.2.1.12.5.114,17.118,21.134.37. trithiolane, 3.5-Dialkyl-1,2,4-trithiolanes; 3-Methyl-5-(2- 138.41.150,53.154.57 octacontane-9,45-dimethanol; 9'-O- methylpropyl)-1,2,4-trithiolane, 3,5-Dialkyl-1,2,4- (2-Hydroxymethyl-2,3,4,5-tetrahydroxycyclopentyl), trithiolanes; 3-(2-Methylpropyl)-1,2,4-trithiolane, 7.8- 2-Oxo-2H-pyran-4,6-dicarboxylic acid, 5.14, 18.22.26.29, Didemethyl-8-hydroxy-5-deazariboflavin, 3,4-Dihydro-46, 33.37.41.50,54,58,62.65,69-Pentadecamethyl-8,1144,47 7-trimethyl-3-3-D-ribofuranosyl-9H-imidazo 1,2-alpurin tetraoxabicyclo68.2.1 triheptacontane-10.46-dimethanol, 9-one, 3,5-Dimethyl-1,2,4-trithiolane, 2,5-Dioxopiperazine 5, 14,18,22,26,29,33,37.4150,54,58,62,65,69-Pentadecam hydrolase, Diphthine, Diphthine; 1'-Amide, 1,2-Diphyta ethyl-8,1144.47-tetraoxabicyclo68.2.1 triheptacontane-10, nylglycerol 3-phosphoinositol, D-myo-Inositol-form, 1.2- 46-dimethanol; 10'-O-(2-Hydroxymethyl-2,3,4,5-tetrahy Diphytanylglycerol 3-phosphoinositol, L-myo-Inositol droxycyclopentyl), 2-O-(3,7,11,15,19-Pentamethyleicosyl)- form, 1,2-Diphytanylglycero-3-phosphoserine, 1.2- 1-O-(3,7,11,15-tetramethylhexadecyl)glycerol, Diphytanylglyceryl-3-phosphorylglycerol, 1.2- Phosphoglycerol geranylgeranyltransferase, O-Phospho Diphytanylglyceryl-3-phosphorylglycerol; 3"-(O- serine Sulfhydrylase, 2-Phosphosulfolactate phosphatase, Methylphosphate) 1,2-Diphytanylglyceryl-3- 1-Phytanoic acid; (3R,7R,11R)-form, Pyroglutamyl pepti phosphorylglycerol: 3"-O-Sulfate, 2.6.9, 13.21.30.38.42.45, dase I, C-L-Rhamnopyranosyl-(1->3)-O-D-galactopyrano 49.57,66-Dodecamethyl-24,27.60.63-tetraoxapentacyclo syl-(1->3)-L-fucose, Serine C-palmitoyltransferase, Sulfo 68.2.1.114,17.134.37.150.53 hexaheptacontane-25,61 halopterin 2. Sulfolobicins, Sulfolobusquinone, dimethanol, 2,6,9,132130,38.42.45,49,57,66 Sulfolobusquinone; Didehydro, Sulfur reductase, Superox Dodecamethyl-24,27.60.63-tetraoxapentacyclo68.2.1.114, ide reductase, 2,6,9,132130,3438,4245,49,53,57,66-Tet 17.134.37.150,53 hexaheptacontane-25,61-dimethanol; 25'- radecamethyl-24,27.60.63-tetraoxatricyclo68.2.1.114.17 O-(2-Hydroxymethyl-2,3,4,5-tetrahydroxycyclopentyl), tetraheptacontane-25,61-dimethanol. 5,14, 18.22.26.29.33, US 2016/01 86168 A1 Jun. 30, 2016

41.50,54,58,62.65,69-Tetradecamethyl-8,1144.47 Acidocin CH5, Acidocins; Acidocin D20079, Acidocins; tetraoxatricyclo[68.2.1.134.37tetraheptacontane-10.46 Acidocin J1 132, Acidocins; Acidocin J 1229, Acidocins; Aci dimethanol, 5, 14,18,22,26,29,33,4150,54,58,62,65,69 docin LCHV. Acidocins; Acidocin LF221A, Acidocins; Aci Tetradecamethyl-8,1144.47-tetraoxatricyclo[68.2.1.134.37 docin LF221B, Acidophilin, Acidophilin 801, Acidophilucin tetraheptacontane-10.46-dimethanol: 46'-O-(2- A, Acinetoferrin, Acireductone synthase, Aclacinomycin M: Hydroxymethyl-2,3,4,5-tetrahydroxycyclopentyl), 10-Epimer, 1-hydroxy, 4C-ketone, Aclacinomycin M. 1-Hy Tetrahydromethanopterin S-methyltransferase, 2.6.9, 13.21. droxy, 4C-ketone, Acnecin, Aconitate methyltransferases; 30,38,4245,49,53,57.66-Tridecamethyl-24,27,60,63-tet trans-Aconitate 2-methyltransferase, Acrylochlorin, Acta raoxatetracyclo68.2.1.114.17.134.37pentaheptacontane gardine A, Actagardine A, N1-Ac, Actagardine A; N1-Ac, 25,61-dimethanol, 2,6,9,132130,38,4245,49,53,57,66 Tridecamethyl-24,27,60,63-tetraoxatetracyclo68.2.1.114, mono-Me ester, Actagardine A; N1-L-Alanyl. Actagardine A. 17.134.37pentaheptacontane-25,61-dimethanol; 25'-O-(2- 11-L-Glutamine, 19-L-cysteinamide analogue, S.S.-dioxide, Hydroxymethyl-2,3,4,5-tetrahydroxycyclopentyl), 6-(3.7, Actagardine A, 15-L-Leucine, 16-L-valine analogue, Acta 11-Trimethyldodecyl)-5-methylbenzobthiophene-4,7- gardine A, 15-L-Leucine, 16-L-valine analogue, S-deoxo, dione, 6-(3.7.11-Trimethyldodecyl)-5-methylbenzob. Actaplanin, Actinobacillin, Actinoidin; Actinoidin A, Acti thiophene-4,7-dione: Homologue (n=3), 6-(3.7.11 noidin; Actinoidin B. Actinomycin lactonase, Actinomycin Trimethyldodecyl)-5-methylbenzobthiophene-4,7-dione: Z1, Actinomycin Z1; 413-Deoxy, Actinomycin Z1; 41B Homologue (n=4), 14.22.26.29.33,41.50,58,62.65,69-Un Deoxy, 413-chloro, Actinomycin Z1; Dideoxy, Actinomycin decamethyl-8, 11,44.47-tetraoxahexacyclo68.2.1.12.5.118, Z1; Dideoxy, 413-chloro, Actinoplanic acid, Actinoplanic 21.134.37.154.57 heptaheptacontane-10.46-dimethanol, acid B. Actinoplanone D, Actinoplanone D; N-Amino, Acti 14.22.26.29.33,41.50,58,62.65,69-Undecamethyl-8,1144, noplanone D; 11-Chloro, Actinoplanone D; 11-Chloro, 47-tetraoxahexacyclo[68.2.1.12.5.118,21.134.37.154,57 N-amino, Actinoplanone D; 11-Chloro, N-(isopropylidene amino), Actinoplanone D; 11-Chloro, N-(3-oxo-2-bute heptaheptacontane-10,46-dimethanol; 10'-O-(2-Hydroxym nylideneamino), Actinoplanone D; N-(3-Oxo-2-butenylide ethyl-2,3,4,5-tetrahydroxycyclopentyl), Uroporphyrinogen neamino), Aculeximycin, Acyl-acyl-carrier-protein III C-methyltransferase, Zeaxanthin; (3R,3'R, all-E)-form, phospholipid O-acyltransferase, Acyl-acyl-carrier-protein: Di-O-O-L-rhamnopyranoside, Zeaxanthin; (3R,3'R, all-E)- UDP-N-acetylglucosamine O-acyltransferase, Acyl-carrier form, Di-O-B-D-glucopyranoside, Zeaxanthin; (3R,3'R, all protein S-acetyltransferase, Acyl-carrier-protein E)-form, 3-O-O-L-Rhamnopyanoside, Zeaxanthin; (3R,3'R, S-malonyltransferase, Acyl-carrer-protein phosphodi 9Z)-form, Di-O-O-L-rhamnopyranoside, Zeaxanthin; (3R, esterase, Acyl-CoA dehydrogenases; cis-2-Enoyl-CoA 3R,9Z)-form, 3-O-O-L-Rhamnopyranoside, Zeaxanthin; reductase (NADPH), Acyl-CoA dehydrogenases; trans-2- (3R,3'R,137)-form, 3-O-O-L-Rhamnopyranoside, Zeaxan Enoyl-CoA reductase (NADPH), Acylglycerol kinase, thin; (3R,3'R,15Z)-form, and 3-O-O-L-Rhamnopyranoside. Acylglycerol lipase, 1-Acylglycerol-3-phosphate O-acyl 0109. In some embodiments, the desired compound is as transferase, N-Acylmannosamine kinase, Acyl phosphate listed below. In some embodiments, the desired compound is hexose phosphotransferase, Adenine deaminase, Adenine as listed below and obtainable from an Eubacteria cell. phosphoribosyltransferase, Adenosine deaminase, Adenosyl Desired compounds include Abaecin, Abequosyltransferase, cobinamide-GDP ribazoletransferase, Adenosylcobinamide Abyssomicin B, Abyssomicin C, Abyssomicin C; Atropiso kinase, Adenosylcobinamide phosphate guanylyltransferase, mer, Abyssomicin C; 8.9-Dihydro, Abyssomicin D, Abysso Adenosylhomocysteine nucleosidase, Adenosylmethionine micin G, Acadesine, Acarbose, Acarbose: 7-O-Phosphate, 8-amino-7-oxononanoate transaminase, Adenosylmethion 2-Acetamidobenzoic acid; Amide, Acetan, Acetate CoA ine hydrolase, Adenylyl-glutamate-ammonia ligase hydro transferase, Acetate kinase, Acetoin:ribose-5-phosphate tran lase, Adenylyl sulfate kinase, Adonixanthin: 3-O-B-D-Glu saldolase, Acetolactate synthase, Acetoxan, Acetylacetone copyranoside, ADP-ribosyl-dinitrogen reductase cleaving enzyme, N-2-4-(Acetylamino)phenyl)-1- hydrolase, ADP-specific glucokinase, ADP-specific phos (hydroxymethyl)-2-(1H-indol-3-yl)ethyl-2.2- phofructokinase, Adriamycin; 11-Deoxy, Aerobactin, Aero dichloroacetamide, Acetyl-CoA C-acetyltransferase, Acetyl cavin, Aerocyanidin, Aeroglycan, Aeruginosin B, C-Agarase, CoA C-acyltransferase, 7-Acetyl-3,4-dihydro-3,6- B-Agarase, Agelaxanthin A; Deoxy, Agglomerin, Agmati dihydroxy-8-methyl-1(2H)-naphthalenone; (-)-form, nase, Agmatine deiminase, Agrastatin, Agrobacteriocin I. Acetylesterase, 3-N-Acetylgalactosaminidase, N-Acetylga Agrobactin, Agrochelin, Agrocin 434, Agrocin 84, Agrocin lactosaminoglycan deacetylase, N-Acetylgalactosaminyl C58, Agrocin D286, Agrocinopin A, Agrocinopin A; De-O- proteoglycan 3-3-glucuronosyltransferase, N-Acetylglu glucopyranosyl, Agrocinopin C, Agrocinopin D. Agropinic cosamine kinase, acid, Ajudazol B, Ajudazol B; 15.29-Didehydro, Akantho N-Acetylglucosaminyldiphosphoundecaprenol N-acetyl-3- mycin, D-Ala-D-Ala dipeptidase, Alanilin, Alanine carbox D-mannosaminyltransferase, N-Acetylglucosaminyldiphos ypeptidase, Alanine dehydrogenase, D-Alanine 2-hydroxym phoundecaprenol glucosyltransferase, 6-O-Acetylglucose: ethyltransferase, B-Alanine pyruvate transaminase, D-form, 6-Acetylglucose deacetylase, Acetylglutamate N-Alanylcysteine; D-L-form, Alanylhomoserinylaspartic kinase, N-Acetylglycine, N-Acetylhexosamine 1-dehydro acid; (all-S)-form, 5-(Alanylhomoserinyl-B-aspartyl)oxy genase, N6-Acetyl-3-lysine transaminase, N-Acetylmu 1,2-dihydro-4-hydroxy-3H-pyrazol-3-one, Alanylphosphati ramoyl-L-alanyl-D-glutamyl-y-diaminoadipic acid, dylglycerol synthase, N-Alanylthreonine: L-L-form, N-(2,3- N-Acetylneuraminate synthase, N-Acetylneuraminic acid; Dihydroxybenzoyl), Albicidin, Albolutein, Albusin B, C.-Pyranose-form, C.(2->8)-Homopolymer, N-Acetylorni Alcaligin, Alcaligin; 8, 18-Dideoxy, Alcanivorone, Aldose thine carbamoyltransferase, Acetylornithine transaminase, B-D-fructosyltransferase, Alirin B1, Alkaline phosphatase, 2-Acetylthiazole, Acetylxylan esterase, Achromobactin, Aci Pseudomonas fluorescens Alkaloid, Alkanal monooxygenase docins, Acidocins; Acidocin 8912, Acidocins; Acidocin A, (FMN-linked), Alkane 1-monooxygenase, Alkanesulfonate Acidocins; Acidocin B, Acidocins; Acidocin 1B, Acidocins; monooxygenase, Alkene monooxygenase, 2-Alkyl-3,4-dihy

US 2016/01 86168 A1 Jun. 30, 2016

ylthio)-1,2,3-cyclopentanetriol: (1R,2R,3R,4S.5R)-form, Antibiotic A 17002A, Antibiotic A 80407A, Antibiotic A 4-Amino-6-(methylthio)-1,2,3-cyclopentanetriol: (1R,2R, 80407A: Diastereoisomer, Antibiotic AB 1, Antibiotic AB 3R.4S.5R)-form, S-Oxide, Aminomethyltransferase, 102, Antibiotic AB 111, Antibiotic AB 113, Antibiotic A 3-Amino-1,4-naphthoquinone-2-carboxylic acid, 2-Amino 17002B, Antibiotic AB 2, Antibiotic A35566B, Antibiotic A 1-(4-nitrophenyl)-1,3-propanediol: (1R,2R)-form, N. Ac, 35566B; 4'-Ketone, Antibiotic AC 1, Antibiotic A 2315C, 2-Amino-1-(4-nitrophenyl)-1,3-propanediol: (1R,2R)-form, Antibiotic A 74.13D, Antibiotic AF 011A1, Antibiotic AF N-Propanoyl, 2-Amino-1-(4-nitrophenyl)-1,3-propanediol; 011A1: Deoxy, Antibiotic AFC-BC11, Antibiotic AH7, Anti (1R,2R)-form, N-(2-Methylpropanoyl), 2-Amino-1-(4-nitro biotic AI 77A, Antibiotic AI 77F, Antibiotic AI 77G, Antibi phenyl)-1,3-propanediol: (1R,2R)-form, N.O3-Di-Ac, otic AM 157, Antibiotic A1-RC 262, Antibiotic AZ-SA-501, 2-Amino-1-(4-nitrophenyl)-1,3-propanediol: (1R,2R)-form, Antibiotic B 1008, Antibiotic 1316B, Antibiotic B 3454, N-Propanoyl, O3-Ac, 2-Amino-1,3-octadecanediol; (2S, Antibiotic B42, Antibiotic B 43, Antibiotic B 4317, Antibi 3R)-form, N-(2R-Hydroxyhexadecanoyl), 2-Amino-4-oxo otic B456, Antibiotic B7, Antibiotic B 90063, Antibiotic B hexanoic acid, 8-Amino-7-oxononanoate synthase, 1371A, Antibiotic B 1371A; 2'-Deoxy, 2',3'-didehydro, Anti 5-Amino-4-oxopentanoic acid, 2-Amino-5-oxo-5-(2-pyridi biotic BA 843, Antibiotic B 1371E, Antibiotic BE 56980, nyl)pentanoic acid: (S)-form, Aminopeptidase I, Aminopep Antibiotic BE 40665A, Antibiotic BE 40665D, Antibiotic BE tidase Y. 7-Amino-1-phenazinecarboxylic acid; N5-Me, 13793X, Antibiotic BK 97A, Antibiotic BL-A60, Antibiotic betaine, 2-Amino-3H-phenoxazin-3-one, 2-Amino-3H-phe BMY 28.190, Antibiotic BN 109, Antibiotic BN 1512, Anti noxazin-3-one; N-Ac, 2-Amino-3H-phenoxazin-3-one; biotic BN 165, Antibiotic BN 175, Antibiotic BN 192, Anti N-B-D-Glucopyranosyl, 2-Amino-3H-phenoxazin-3-one: biotic BN 200, Antibiotic BN 225, Antibiotic BN 7, Antibi 6-Hydroxy, 5-(2-Aminophenyl)-5-oxopentanoic acid, 3-(2- otic BN 240B, Antibiotic BO7, Antibiotic BSA, Antibiotic Aminophenyl)pyrrole, 2-Amino-2-propenoic acid, N-(3- BU4514N, Antibiotic 6108C, Antibiotic 66-40C, Antibiotic Aminopropyl)-1,5-pentanediamine, N-(5-Amino-1-f-D-ri CB 25-1, Antibiotic CB 25-11, Antibiotic C 33196E4, Anti bofuranosylimidazole-4-carbonyl)-L-aspartic acid biotic C 33196E6, Antibiotic C 33196E7, Antibiotic C 5'-phosphate, 2-Amino-6-(1,2,3,4-tetrahydroxybutyl)-4 33196E4R, Antibiotic C33 196E6R, Antibiotic C33 196E7R, (1H)-pteridinone; (1S,2S,3R)-form, 2-Amino-3-(2,4,5-tri Antibiotic C 11924F1, Antibiotic CF 661, Chainia hydroxyphenyl)propanoic acid: (S)-form, 2-Amino-6-(1,2,3- minutisclerotica Antibiotic, Antibiotic CP 37277, Antibiotic trihydroxypropyl)-4-(1H)-pteridinone; (1S,2S)-form, 5.6R, CP3.7932, Antibiotic CP 40042, Antibiotic CP 41012, Anti 7,8-Tetrahydro, 4-Amino-N.N.N-tris(3-aminopropyl)-1- biotic CP 41043, Antibiotic CP 41494, Antibiotic CP 42752, butanaminium, 5-Aminovalerate transaminase, Ammonificin Antibiotic CP 43038, Antibiotic CP 43139, Antibiotic CP A, Ammonificin A; 4'-Deoxy. 4'-bromo, Ammonigenin, 43334, Antibiotic CP43596, Antibiotic CP 44161, Antibiotic Amonabactin P 693, Amonabactin P 750, Amonabactin T CP48926, Antibiotic CP 48927, Antibiotic 6108D, Antibiotic 732. Amonabactin T 789, Amphibactins, Amphibactins: 67-121D, Antibiotic DC 102: Demethoxy, 12,13-didehydro, Amphibactin C, Amphibactins; Amphibactin D, Amphibac Antibiotic DC 5-4, Antibiotic DOB 41, Antibiotic FM 1001, tins; Amphibactin E, Amphibactins: Amphibactin F, Antibiotic FR 183737, Antibiotic FR 183742, Antibiotic FR Amphibactins; Amphibactin H. Amphisin, Amphisin; 9-L- 900493, Antibiotic FR 90.1375, Antibiotic FR 901451, Anti Glutamic acid analogue, Amphomycin, AMP nucleosidase, biotic FR 901463, Antibiotic FR 901465, Antibiotic FR C.-Amylase, 3-Amylase, Amylocyclicin A, Amylosin, Amy 901465; 2-Deoxy, Antibiotic FR 901484, Antibiotic FR losucrase, Amylovoran, Amylovonin L. Analysine, Andrim 901537, Antibiotic FU 10, Antibiotic G 1499-2, Antibiotic G ide, Andrimide: 3-Epimer, 3-hydroxy, Angiolam A. Angi 2A, Antibiotic GE 2270, Antibiotic GE 2270; Antibiotic GE olam A. 9", 10-Dihydro, Angiolam A; 6'-Ketone, 2270A, Antibiotic GIF1, Antibiotic GIF2, Antibiotic GTRI Angucyclinone R2, Anguibactin, 3.6-Anhydro-2-deoxyglu BB, Antibiotic H 107, Antibiotic 477-2h, Antibiotic HA 106, cose: D-form, Anhydrorhodovibrin, Anhydrorhodovibrin; Antibiotic HA 135, Antibiotic HA 145, Antibiotic HA 176, O-De-Me, O-B-D-glucopyranoside, Anhydrorhodovibrin; Antibiotic HC 62, Antibiotic HM 17, Antibiotic HP 17, Anti O-De-Me, O-11-methyldodecanoyl-(->6)-B-D-glucopyra biotic 480HS20, Antibiotic HUT57, Antibiotic 11, Antibiotic noside, Anhydrorhodovibrin; O-De-Me, Ansatrienin B; IB 96212, Antibiotic I-SKA1, Antibiotic I-SKB1, Antibiotic 20-O-B-D-Glucopyranoside, Ansatrienin B; 4"-Hydroxy, I-SKB2, Antibiotic JA 20, Antibiotic JI 20A, Antibiotic JI Ansatrienin B; 20.23-Quinone, 19-hydroxy, Ansatrienin B; 20B, Antibiotic K52A, Antibiotic K252b, Antibiotic K252b: 20.23-Quinone, 4'-hydroxy, Antascomicin B, Antascomicin Me ester, Antibiotic K 52B, Antibiotic KBS, Antibiotic K B; 30-Deoxy, Antascomicin B; 30-Deoxy, 37-hydroxy, 144e, Antibiotic K144g, Antibiotic KG 431A, Antibiotic KM Antascomicin B; Lower homologue, 30-deoxy, Antascomi 8, Antibiotic KT 6291, Antibiotic L 13365, Antibiotic L cin B; 31-Me ether, Anthranilate oxygenases; Anthranilate 660631: (1R,4S.5R)-form, Antibiotic LIA 0371, Antibiotic 1.2-dioxygenase (deaminating, decarboxylating), Anthra LIA 0677, Antibiotic LIA 0725, Antibiotic LIA 0185 I, Anti nilate phosphoribosyltransferase, Anthraniloyl-CoA biotic LIA 0725-II, Antibiotic LI-F, Antibiotic LL-AB 664, monooxygenase, Periplaneta americana Antibacterial pep Antibiotic LL-AB 664; N5-Me, Antibiotic LL-BO 1208C, tides, Antibiotic 02-8, Antibiotic 13-384-5, Antibiotic Antibiotic LL-BO 1208B, Antibiotic LL-D O5139B, Antibi 13-384-5; N-Hydroxy, Antibiotic 1569, Antibiotic 1998, otic LL-EM 0103, Antibiotic LP 1, Antibiotic M101, Anti Antibiotic 2725, Antibiotic 30-2, Antibiotic 339-29, Antibi biotic M 138, Antibiotic M27, Antibiotic M741, Antibiotic otic 388, Antibiotic 4205, Antibiotic 61-26, Antibiotic M9026, Antibiotic M92, Antibiotic MA 18, Antibiotic M 68-1147, Antibiotic 681-17, Antibiotic 696, Antibiotic A 53A2, Antibiotic M 53B1, Antibiotic M 53B2, Antibiotic 10947, Antibiotic A 12918, Antibiotic 2197A, Antibiotic A MBM 1212, Antibiotic MF 205, Antibiotic MM 240, Antibi 287, Antibiotic A 39893, Antibiotic A 477, Antibiotic otic MM 42842, Antibiotic MSDA 63 A, Antibiotic MX-A, 67-121A, Antibiotic 67-121A. N-De-Me, Antibiotic Antibiotic N 1999A2, Antibiotic NK 11629, Antibiotic NP 67-121A; 4'-O-O-D-Mannopyranosyl, Antibiotic A 672, 023, Antibiotic OM 001, Antibiotic P 19, Antibiotic P 2, Antibiotic A 6984, Antibiotic A 7413, Antibiotic A 84575, Antibiotic P3, Antibiotic P4, Antibiotic P40, Antibiotic PA US 2016/01 86168 A1 Jun. 30, 2016 22

2046, Antibiotic PA5, Antibiotic PA7, Antibiotic PB5266A, 16.20-Dideoxy, Apoptolidin A; 2'-Epimer, 16.20-dideoxy, Antibiotic PB 5582A, Antibiotic PB 52668, Antibiotic PB Apoptolidin A; 2'-Epimer, 16.20-dideoxy, 27-O-deglycosyl, 5266C, Antibiotic Pep 5, Antibiotic PM 94.128, Antibiotic R Apramycin, Aqabamycin G, Aquachelins, Aqualysin 1, Ara 176502, Antibiotic RK 0721, Antibiotic S 264; Antibiotic S binan endo-1,5-O-L-arabinosidase, Arabinitol, D-form, 264A, Antibiotic S 264; Antibiotic S 2648, Antibiotic S 264; 1-Phosphate, Cl-N-Arabinofuranosidase, Arabinogalactan Antibiotic S 264C, Antibiotic S 53210A, Antibiotic S endo-1,4-B-galactosidase, Arabinokinase; D-form, D-Ara 54832A, Antibiotic SB 219383, Antibiotic Sch 20561, Anti binonolactonase, L-Arabinonolactonase, Aralkylamine biotic Sch 20561; 32-O-O-D-Glucopyranoside, Antibiotic dehydrogenase, Archaeol: 1-O-B-D-Galactofuranosyl-(1- Sch 23831, Antibiotic Sch. 37137, Antibiotic Sch 38519, >6)-D-galactofuranoside, Archaeol: 1-O-O-D-Galactopyra Antibiotic Sch 40832, Antibiotic Sch. 419558, Antibiotic Sch noside, Archaeol: 1-O-O-D-Glucopyranosyl-(1->2)-(6-O- 419559, Antibiotic Sch42137, Antibiotic Sch42137; 11-Ac, acetyl-B-D-galactofuranoside), Archaeol; 1-O-C-D- Antibiotic Sch. 42137: 14-Ac, Antibiotic Sch 49088, Antibi Glucopyranosyl-(1->2)-B-D-galactofuranoside, Archaeol; otic Sch 54445, Antibiotic Sch. 56036, Antibiotic SE 73, 3'R-Hydroxy, Archaeol: 3"R-Hydroxy, Archaeol: 3"-Hy Antibiotic SE 74, Antibiotic SE 73-74D, Antibiotic SF 1908, droxy, 1-O-B-D-galactopyranosyl-(1->6)-B-D-galactopyra Antibiotic SF 1919, Antibiotic SF 2033, Antibiotic SF 2107, noside, Archaeol. 3"-Hydroxy, 1-O-B-D-galactopyranosyl Antibiotic SF 2107; Antibiotic SF 2107A1, Antibiotic SF (1->6)-B-D-glucopyranosyl-(1->3)-3-D- 2107; Antibiotic SF 2107A2, Antibiotic SF 2107; Antibiotic galactopyranoside, Archaeol: 3"-Hydroxy, 1-O-B-D- SF 21078, Antibiotic SF 2107; Antibiotic SF 2107C, Antibi glucopyranoside, Archaeol; 1-O-O-D-Mannopyranosyl-(1- otic SF 2132, Antibiotic SF 2139, Antibiotic SF 2240, Anti >3)-B-D-galactopyranoside. Archaeol; 1-O-C-D- biotic SF 2309, Antibiotic SF2312, Antibiotic SF 2339, Anti Mannopyranosyl-(1->2)-O-D-glucopyranoside, biotic SF 2381, Antibiotic SF 2448; Antibiotic SF 2448A, Archazolide A, Archazolide A: 15-O-B-D-Glucopyranoside, Antibiotic SF 2448; Antibiotic SF 2448B, Antibiotic SF Archazolide A: 7-O-B-D-Glucopyranoside, Archazolide A: 2448; Antibiotic SF 2448C, Antibiotic SF 2513; Antibiotic 26-Hydroxy, 7-O-B-D-glucopyranoside, Archazolide B, Arc SF 2513A, Antibiotic SF 2513; Antibiotic SF 25138, Antibi hazolide B: A3-Isomer(E-), Arcyriaflavin A, Arcyriaflavin A; otic SF 2513; Antibiotic SF 2513C, Antibiotic SF 2423A, 2,10-Dihydroxy, Arcyriarubin A, Arginase, D-Arginase, Antibiotic SF 21978, Antibiotic SF 23158, Antibiotic SPF Arginidiene, Arginine: (S)-form, N-Tetradecanoyl, Arginine; 1012, Antibiotic SQ26180; (R)-form, Antibiotic SQ28502, (S)-form, N-Pentadecanoyl, Arginine: (S)-form, N-Hexade Antibiotic SQ 28504, Antibiotic SQ 28516, Antibiotic SQ canoyl, Arginine, (S)-form, N-(9Z-Hexadecenoyl), Arginine 28516; 6'-Amide, Antibiotic SQ 28546, Antibiotic SS 237, deiminase, Arginine N-succinyltransferase, Argyrins, Argy Antibiotic SS 228B, Antibiotic SS 228Y, Antibiotic SU1, rins; Argyrin A, Argyrins; Argyrin B, Ariakemicin A, Ariake Antibiotic SU2, Antibiotic SU2: 5-Deoxy, Antibiotic SU2: micin A; A11-Isomer, Aridicin, Aridicin; Aridicin A, 6A-Al 6'-N-Me, Antibiotic 1024 SY 1, Antibiotic TAN 1054; Anti cohol, Aridicin; Aridicin B, 6A-Alcohol, Aridicin; Aridicin biotic TAN 1054A, Antibiotic TAN 1054: Antibiotic TAN C1, 6A-Alcohol, Aridicin; Aridicin C2, 6A-Alcohol, Aridi 1054B, Antibiotic TAN 1511, Antibiotic TAN 1713, Antibi cin; Aridicin D, 6A-Alcohol, Aristeromycin, Arizonin C1, otic TAN 425, Antibiotic TAN 456, Antibiotic TAN 643, Arizonin C1, O7-De-Me, Arizonin C1; O8-De-Me, Arizonin Antibiotic TAN 667, Antibiotic TAN 850, Antibiotic TAN C3, Arizonin C3; 4.8-Di-O-de-Me, Arizonin C3; 4.9-Di-O- 883, Antibiotic TAN 422A, Antibiotic TAN 1057C, Antibi de-Me, Arogenic acid, Aromatic amino acid transaminases; otic TAN 10570; 2-Epimer, Antibiotic TM743, Antibiotic TP Aromatic amino acid transaminase, Arphamenine A, Arpha 1161, Antibiotic TPU 0043; Stereoisomer (1), Antibiotic T menine A, 4-Hydroxy, Arsenate reductases; Arsenate reduc 23W, Antibiotic UAA3, Antibiotic UFC 3930, Antibiotic UK tase (aZurin), Arsenate reductases; Arsenate reductase (do 68597, Antibiotic WA 3909, Antibiotic WAP 4068A, Antibi nor), Arsenate reductases; Arsenate reductase (glutaredoxin), otic WAP 8294A, Antibiotic WB 3559A. Antibiotic WB Arsindoline A, Arthrobacilin; Arthrobacilin A, Arthrobacilin; 35598, Antibiotic WB 3559C, Antibiotic WS 790898, Anti Arthrobacilin B, Arthrobacilin; Arthrobacilin C, Arthrobac biotic WS 79089B; S-Lactone, 6-Ac, Antibiotic WS 79089B; terin, Arthrobactin, Arthrofactin, Arugomycin; 7-(Deglyco 8-Lactone, Antibiotic WSS 2217, Antibiotic WSS 2219, Anti syloxy), 3C O-de-Me, Arylsulfatase, Aryl-sulfate sul biotic WSS 2219;4"-Deoxy, Antibiotic WSS 2220, Antibiotic fotransferase. A 23S, Asparaginase, Asparagine; (S)-form, WSS 2221, Antibiotic WSS 2222, Antibiotic XK 206, Anti N2-(9-Methyldecanoyl), Asparagine: (S)-form, N2-(10-Me biotic XK209, Antibiotic Y1, Antibiotic Y 02039H, Antibi thylundecanoyl), Asparagine: (S)-form, N2-(11-Methyl otic Y 02910-IB, Antibiotic YI-HU1, Antibiotic YI-HU3, dodecanoyl), Aspartate carbamoyltransferase, Aspartate Antibiotic Y 03559J-A, Antibiotic YL 02107O-A, Antibiotic kinase, Aspartate oxidases; L-Aspartate oxidase, Aspartate YL 02107O-A; 6C-Hydroxy, Antibiotic YL 02107O-A: phenylpyruvate transaminase, Aspartate transaminase, 11-O-Deacyl, Antibiotic YL 02107O-B, Antibiotic YM Aspartic acid: (S)-form, Aspartyl aminopeptidase, L-Aspar 47515, Antibiotic Y 0546OM-A, Antibiotic YM 32890A, tyl-L-N2-hydroxyaspartyl-D-cycloserine, B-Aspartyl pepti Antibiotic YM 32890A; A23,25,27-Isomer, Antibiotic YS dase, Astaxanthin; (3S,3'S)-form, 3-O-B-D-Glucopyrano 822A, Anticapsin, Streptoverticillium Anticoagulant, Anti side, ATP phosphoribosyltransferase, Aurachin A, Aurachin fungal CB-1, Antifungin, Propionibacterium jensenii Anti A: 3 (3-Hydroxy, Aurachin B, Aurachin D, Aurachin D: 95 microbial peptide, Antimycin A; Antimycin A18, Antlermi Hydroxy, Aurachin D; N-Hydroxy, Aurachin E, Aurachin F, cin B, Antlermicin C, Antlermicin D, Apicularen A, Aurachin G, Aurachin G: 1,2'-Dihydro, Aurachin G: ApicularenA, 4-O-(2-Acetamido-2-deoxy-3D-glucopyrano 35-Methoxy, 1,2-dihydro, Aurachin K, Aurachin K: 3,4- side), 8-Apo-(3-caroten-8-al; 8-Carboxylic acid, 8-Apo-B- Didehydro, 1,2-dihydro, Aurafurone A, Aurafurone A: caroten-8-al; 8'-Carboxylic acid, Me ester, 8-Apo-p-caro 7-Deoxy, 6,7-didehydro(E-), Aurafurone A; 8E-Isomer, ten-8-oic acid; (all-E)-form, 12-Methyltetradecanoyl-(->6)- 7-deoxy, 6,7-didehydro(E-), Aurantinin A, Aurantinin A; C-D-glucopyranosyllester, Apoptolidin A, Apoptolidin A; 17-O-(6-Deoxy-B-ribohexopyranos-3-ulosyl), Aureocins: 6-Demethyl, Apoptolidin A; 16-Deoxy, Apoptolidin A; Aureocin A53, Aureocins: Aureocin A70, Aureothin; (R)- US 2016/01 86168 A1 Jun. 30, 2016

form, AUS 1. Autoinducer 2, Staphylococcus aureus Autoin form, 35-Carboxylic acid, (35->32)-lactone, 32.33,34,35 ducing peptide 1, Staphylococcus aureus Autoinducing pep Bacteriohopanetetrol; (21C.H.325.335.345)-form, 32.33.34. tide 2, Staphylococcus aureus Autoinducing peptide 3. 35-Bacteriohopanetetrol; (21 BH.32R,33R,34R)-form, Staphylococcus aureus Autoinducing peptide 4. Staphyllo 32.33,34,35-Bacteriohopanetetrol; (21 BH.225,295,305,335, coccus epidermidis Autoinducing peptide, Staphylococcus 345)-form, 32-Ketone, 35-O-(2-amino-2-deoxy-B-D-glu intermedius Autoinducing peptide, Staphylococcus lugdun copyranoside), Bacteriophaeophorbide a, Bacterioruberin; ensis Autoinducing peptide, Avicin A, Avoparcin; B-Avopar 3"-Deoxy. 2",3'-didehydro, 3',4'-dihydro, Bacterioruberin; cin, O-Demannosyl, O2B-Me, Avoparcin; B-Avoparcin, 3"-Deoxy. 2",3'-didehydro. 3',4'-epoxide, Bacterioruberin; O2B-Me, AVS, 5-AZacytidine, 8-AZainosine, AZaserine: (S)- 3",3"-Dideoxy. 2",3":2",3"-tetradehydro, Bacterioruberin; form, 2-AZetidinecarboxylic acid: (S)-form, 3-AZetidinone; 3'3"-Dideoxy. 2",2",3",3"-tetradehydro,3,3'44'-tetrahy Covalent hydrate, Azotobactin CCM2798, Azotobactin D, dro, Bacterioruberin; 13Z-Isomer, Bacterioruberin; 5Z.9"Z- Azotobactin G173, Azotobactin 87-I, Azotobactin 87-I; Isomer, Bacterioruberin; 5Z-Isomer, Bacterioruberin; Y-Lactone, Azotobactin P19, Azotobactin Pch9446, Azotoch 9Z-Isomer, Bacteroplanecin, Bacthuricins, Bacthuricins; elin, AZOverdin A, AZOverdin A; 4'-Amide, AZOverdin G, Bacthuricin F103, Bactobolin A, Bactobolin A; Nc)-(Alany AZOverdin G; 5 B,6-Dihydro, Azoxybacilin; (Z.S)-form, lalanyl), Bactobolin A: No-Alanyl, Bactobolin A; 5-Deoxy, Azureomycin, B 12489, Bac 1829, Bacereutin, Baciferacin, Bactobolin A; 5-Deoxy, Nc)-alanyl, Bactobolin A; 5-Deoxy, Bacileucine A, Bacileucine B. Bacilipin, Bacillaene, Bacil Nc)-(alanylalanyl), Bactobolin A; 5-Deoxy, dechloro, Bacto laene; 14,15-Dihydro, Bacillaene; 2"-O-B-D-Glucopyrano bolin A; 5-Deoxy, dechloro, Nc)-alanyl, BAF. Bagougeram side, Bacillamide A, Bacillamide A, 15R-Alcohol, Bacilla ine A, Bagougeramine B, Bamylocin A, Bavaricins, Bavar mide A: 15-Deoxo, 15R-acetamido, Bacillibactin, icins; Bavaricin A, Bavaricins; Bavaricin MN, BE 40644, Bacillistatin 1, Bacillistatin 2, Bacilithiol, Bacillocin, Bacil Benastatin A; 5,6-Dihydro, 11-O-sulfate, Benastatin A; locin 490, Bacillocins; Bacillocin 1580, Bacillocins; Bacil 11-O-Sulfate, Benzenecarbothioic acid; SH-form, Meester, locin 490, Bacillocins; Bacillocin 602, Bacillocins; Bacillo 1.2-Benzenedicarboxylic acid; Monobutyl ester, Benzene cin B37, Bacillocins; Bacillocin Bb, Bacillolysin, 1,2-dioxygenase, Benzeneethanethioic acid; SH-form, S-Me Bacillomycin A, Bacillomycin C, Bacillomycin D: Bacillo ester, Benzenesulfonamide: N-Butyl, 1.2-Benzisoxazole-3, mycin D1, Bacillomycin D: Bacillomycin D2, Bacillomycin 6-diol, Benzoate oxygenases; Benzoate 1,2-dioxygenase, D; Bacillomycin D3, Bacillomycin D; Bacillomycin D4, Benzoic acid, BenZophenone, p-Benzoquinone reductase, Bacillomycin D; Bacillomycin D5, Bacillomycin F. Bacillo 2,6-Benzothiazolediol; NH-form, N-Me, 2(3H)-Benzothia mycin Fb. Bacillomycin Fc, Bacillomycin LC, Bacillomycin Zolethione, 2-Benzothiazolol, Benzoyl-CoA 3-monooxyge P: Bacillomycin P1, Bacillomycin P: Bacillomycin P2, Bacil nase, Benzoyl-CoA reductase, 5-Benzyl-3-hydroxy-2-iso lomycin S. Bacillopeptin, Bacilosarcin A, Bacilosarcin B, propylpyrazine, 5-Benzyl-3-hydroxy-2-isopropylpyrazine; Bacilysin, Baciphelacin, Bacircines, Bacisubin, Bacitracin, 4-Hydroxy, 5-Benzyl-3-hydroxy-4-phenyl-2(5H)-furanone; Bacitracin B, Bacitracin C, Bacitracin D, Bacitracin G, Bac (+)-form, 5-Benzyl-3-hydroxy-4-phenyl-2(5H)-furanone; terial leucyl aminopeptidase, Bacteriochlorophyll a, Bacte (+)-form, Meether, 2-Benzyl-3-hydroxypyrazine: OH-form, riochlorophyll b, Bacteriochlorophyll b; 10.11'-Didehydro, Me ether, 3-Benzylidene-6-isobutylidene-2.5-piperazinedi Bacteriochlorophyll c, Bacteriochlorophyll d. Bacteriochlo one: (Z.Z)-form, 4"-Methoxy, 3-Benzylidene-6-isobutyl rophyll e, Bacteriochlorophyll g. Bacteriochlorophyll g; idene-2,5-piperazinedione; (2Z.5E)-form, 4"-Methoxy, 21-Epimer, Bacteriochlorophyllidea, Bacteriocin 217, Bac 4-Benzyl-3H-pyrrolo2.3-cquinoline, 4-Benzyl-3H-pyrrolo teriocin 28, Bacteriocin 31, Bacteriocin 41, Bacteriocin 51, 2,3-cquinoline: 4-Hydroxy, 2-Benzyl-4(3H)-quinazoli Bacteriocin ABP 118, Bacteriocin AS 48, Bacteriocin 14B, none, Bergaptol; Meether, Betaine reductase, Bi-(4'-O-3)- Bacteriocin 28b, Bacteriocin Bc48, Bacteriocin C3603, Bac daidzein, Bifidobacterin, Bifidocin B, 3',5-Bigenistein, Bile teriocin E1, Bacteriocin E50-52, Bacteriocin GMO05, Bacte acid-CoA hydrolase, Biocerin, Biostim, Biotin synthase, riocin HV219, Bacteriocin I1, Bacteriocin J46, Bacteriocin Biphenyl-2,3-diol 1.2-dioxygenase, Biphenyl 2,3-dioxyge JW 15BZ, Bacteriocin L 1077, Bacteriocin LL 171, Bacte nase, N,N'-Bis(4-aminobutyl)-1,4-butanediamine, N.N-Bis riocin LS1, Bacteriocin Mc-E22, Bacteriocin MMFII, Bac (3-aminopropyl)-1,4-butanediamine, N,N-Bis(3-aminopro teriocin N5, Bacteriocin NB-C1, Bacteriocin PPK34, Bacte pyl)-1,4-butanediamine; N4-Ac, 2.5-Bis(4-hydroxybenzyl) riocin PsWP-10, Bacteriocin R 1333, Bacteriocin Rim-10, pyrazine, Bis(2-hydroxyethyl) trisulfide, 2.7-Bis(4-hydroxy Bacteriocin S34, Bacteriocin SJ, Bacteriocin SM19, Bacte 3-methyl-2-butenyl)-3, B-carotene, 2,2'-Bis(4-hydroxy-3- riocin Smb, Bacteriocin ST44AM, Bacteriocin ST 151BR, methyl-2-butenyl)-B.B-carotene; O-B-D-Glucopyranoside, Bacteriocin ST5EHa, Bacteriocin ST 23LD, Bacteriocin ST16 3,4-Bis(4-hydroxyphenyl)-1H-pyrrole-2,5-dicarboxylic Pa, Bacteriocin T8, Bacteriocin TH14, Bacteriocin TN 635, acid, 3,4-Bis(4-hydroxyphenyl)-1H-pyrrole-2,5-dicarboxy Bacteriocin UO004, Bacteriocin UviB, 32,33,34,35-Bacte lic acid; 4'-Deoxy. 2.5-Bis(1H-indol-3-ylmethyl)pyrazine, riohopanetetrol; (21 BH.32R,33R,34S)-form, 32.33,34,35 1.2-Bis(2-methoxyethoxy)ethane, 2.5-Bis(2-methylpropyl) Bacteriohopanetetrol; (21 BH.32R,33R,34S)-form, pyrazine, 3,6-Bis(2-methylpropyl)-2(1H)-pyrazinone; 35-Deoxy, 35-amino, 32.33.34.35-Bacteriohopanetetrol; OH-form, Me ether, Bisnorbiotin; (3S,4S,5S)-form, (21 BH.32R,33R,34S)-form, 35-Deoxy, 35-(ornithylamino), Bispolide A1, Bispolide A1: 13,13'-Di-Meether, Bispolide 32.33,34,35-Bacteriohopanetetrol; (21 BH.32R,33R,34S)- A1: 2"-Hydroxy, Bispolide A1: 2"-Hydroxy, 13,13'-di-Me form, 35-Deoxy, 35-(tryptophanylamino), 32.33.34.35-Bac ether, Bispolide A1: 2"-Hydroxy, 13-Meether, Bispolide A1; teriohopanetetrol; (21 BH.32R,33R.34S)-form, 35-O-B-D- 2"-Hydroxy, 13'-Meether, Bispolide A1; 13-Meether, 2.5- Glucuronopyranoside, 32.33.34.35-Bacteriohopanetetrol; Bis(1,2,3,4-tetrahydroxybutyl)pyrazine; (15.1"S.25.2"5.3'S, (21 BH.32R,33R,34S)-form, 35-Deoxy, 35-(N-hexadecanoy 3"S)-form, 2.2"-Bis-O-(2-acetamido-2-deoxy-B-D-glucopy lamino), 32.33.34.35-Bacteriohopanetetrol; (21 BH.32R, ranoside), Bisucaberin, BK 101, BK 101; IBK 101C, 33R,34S)-form, 35-Deoxy, 35-(N-87-hexadecenoylamino), Blasticidin S; 3"-N-Leucyl, Blastmycetin A, Blastmycetin B, 32.33,34,35-Bacteriohopanetetrol; (21 BH.32R,33R,34S)- Blastmycetin B; 3-Deoxy, Blastmycetin B; 3-Epimer, Blast US 2016/01 86168 A1 Jun. 30, 2016 24 mycetin B; 3-Epimer, 3-deoxy, Blastmycetin D, Blastmyce monooxygenases; Camphor 1.2-monooxygenase, Camphor tin E. Blastmycetin F. Blastolysin, Bleomycin; Bleomycin monooxygenases; Camphor 5-monooxygenase, Candiplane A5, Bleomycin hydrolase, Blood-group-substance endo-1,4- cin, C5a peptidase, Capistruin, Capreomycin, Capsular B-galactosidase, Blue copper proteins; Amicyanin, Blue cop polysaccaride endo-1,3-O-galactosidase, Carbamate kinase, per proteins; AZurin, Blue copper proteins; PseudoaZurin, N6-(Carbamoylmethyl)-2'-deoxyadenosine, Carbazomycin Blue copper proteins; Rusticyanin, Bogorol A, Bogorol B, G. Carbazomycin G: 6-Methoxy, 1-(B-Carbolin-1-yl)-3-hy Bogorol C, Bogorol D. Bogorol D: S-Oxide, Bohemamine, droxy-1-propanone, Carbon monoxide dehydrogenases; Car Boivin substance, Bongkrekic acid; (20E)-form, Bongkrekic bon monoxide dehydrogenase (acceptor), Carbon monoxide acid; (20Z)-form, Boticins, Botrocidin, Botryticidin A, Bot dehydrogenases; Carbon monoxide dehydrogenase (cyto tromycin, Botulinum Toxins, Bovicins; Bovicin 255, Bov chrome b-561), Carbon monoxide dehydrogenases; Carbon icins; Bovicin HC5, Bovicins; Bovicin HJ50, Boxazomycin monoxide dehydrogenase (ferredoxin), 1-(2-Carboxya A, Boxazomycin A; 1"-Deoxy, Boxazomycin A; 5-Deoxy, nilino)-1-deoxyribulose: D-form, 2-Carboxy-2,5-dihydro-5- Bozacin 14, Bradyoxetin, Branched-chain amino acid tran oxo-2-furanacetic acid; (R)-form, 7-Carboxy-8-(2,6-dihy saminase, Branched-chain fatty acid kinase, Branched-dext droxybenzoyl)-4-oxo-2-propyl-4H-1-benzopyran-5-acetic ran exo-1,2-O-glucosidase, Brassicanal B. Brassicanal C. acid, 3-Carboxyethylcatechol 2,3-dioxygenase, 3-O-(1-Car Brassinin, Brassinin; N1-Methoxy, Brassining 4-Methoxy, boxyethyl)glucuronic acid; D-(1R)-form, 4-O-(1-Carboxy Brassitin, Brassitin: 1-Methoxy, Bravomicin A, Bravomicin ethyl)glucuronic acid; D-(1S)-form, N6-(1-Carboxyethyl) A: Etester, Bravomicin A; 6-Hydroxy, Bravomicin A; 6-Hy lysine; (S,S)-form, N5-(Carboxyethyl)ornithine synthase, droxy, Me ester, Bravomicin A; Me ester, Bravomicin D, Carboxymethylenebutenolidase, Carboxypeptidase T. Car Bravomicin D: Et ester, Bravomicin D; Me ester, Bresein, boxypeptidase Taq, Carnobacteriocins, Carnobacteriocins; Brevicins; Brevicin 27, Brevicins; Brevicin 286, Brevicins; Carnobacteriocin A, Carnobacteriocins; Carnobacteriocin Brevicin 37, Brevicins; Brevicin 925A, Brevicins; Brevicin B1, Carnobacteriocins; Carnobacteriocin B2, Carnobacterio AF01, Brevicins; Brevicin SD-22, Brevicins; Brevicin SG1, cins; Carnobacteriocin BM1, Carnocins; Carnocin 54, Car Brevimycin, Brevin, Brevinic acid, Brevistin, Brevolin, Bro nocins; Carnocin CP 5, Carnocins; Carnocin H, Carnocins; chocin C, Bromoalterochromide A, 6-Bromo-1H-indole-3- Carnocin KZ213, Carnocins; Carnocin UI49, Carnocyclin A, carboxaldehyde, Brucellacin, Bulbiformin, Bulgarican, Carnosin 44A, Carocin D. Carocin S2, Carolactone, Bf3 Bulgecin A, Bulgecin B, Bulgecin C, Burkholdac A. Burkhol Carotene-2,3-diol; (2R,3R)-form, B, up-Carotene-2,3-diol; dac B, Burkholdac B; 4"-De(methylthio), 4"-ethyl, Burkhol (2R*,3R)-form, B.up-Caroteine-4,4'-dione, Y-Carotene; 1,2'- dac B; 4"-S-Oxide, Burkholdine 1097, Burkholdine 1097: Dihydro, Carotovoricin, L-Carrageenase, K-Carrageenase, 7-O-B-D-Xylopyranoside, 1,4-Butanediamine, 1,4-Butane w-Carrageenase, Caryophyllan, Caryophyllose, Caryose, diamine; N-(2,3-Dihydroxybenzoyl), 1,4-Butanediamine: Caseicin 80, Caseicins, Catacandin; Catacandin A, Catalase, N-Hexadecanoyl, Butanethioic acid; SH-form, S-Me ester, Catechol dioxygenases; Catechol 1,2-dioxygenase, Catechol 1-Butanol, 3-Butanoyl-1,4a, 12.12a-tetrahydro-1,4,4a,6,7- dioxygenases; Catechol 2,3-dioxygenase, CDP-4-dehydro pentahydroxy-2,5-naphthacenedione, 2-(2-Butenyl)ben 6-deoxyglucose reductase, CDP-diacylglycerol-glycerol-3- Zenehexanoic acid, 2-(2-Butenyl)benzenehexanoic acid; phosphate 3-phosphatidyltransferase, CDP-diacylglycerol 1,2'-Didehydro, 2-(2-Butenyl)benzenehexanoic acid; 1",4'- serine O-phosphatidyltransferase, CDP-glycerol glycero Didehydro, 2-(2-Butenyl)benzenehexanoic acid; A1"-Isomer phosphotransferase, CDP-ribitol ribitolphosphotransferase, (Z-), 1-Butoxy-2-methyl-1-(2-methylpropoxy)-2-propanol, Cellobiose phosphorylase, Cellodextrin phosphorylase, Cel Butyl methyl disulfide, 2-Butyl-5-propyl-1,3-benzenediol, lulase, Cellulose 1,4-B-cellobiosidase, Cellvibriocin, Eubac Butyltrimethylpyrazine, Butyrate acetoacetate CoA-trans terium saburreum Cell-wall antigen, Cell wall protein, Cepa ferase. Butyrate kinase, Butyricin 7423. Butyrivibriocin, ciachelin, Cepaciamide A, Cepaciamide B, Cepacian, Butyrivibriocin; Butyrivibriocin AR10, Butyrivibriocin: Cepacidin A1, Cepacidin A1; 1"-Deoxy, Cepacin A, Cepacin Butyrivibriocin OR435, Butyrivibriocin; Butyrivibriocin B, Cepalycin, Cephabacin F; Cephabacin F4, Cephabacin F; OR79A, Cadeguomycin; Nitrile, Caerulomycin E: 1'-Car Cephabacin F4, N27-L-Seryl, Cephabacin F; Cephabacin F4, boxylic acid, amide, Caerulomycin E: 1'-Carboxylic acid, N27-(L-Seryl-L-alanyl), Cephabacin F; Cephabacin F4, N-methoxyamide, Caerulomycin E: 1'-Carboxylic acid, 28-Deoxy, N27-L-alanyl, Cephabacin F; Cephabacin F4, nitrile, Caerulomycin E: O-De-Me, E-oxime, Caerulomycin 28-Deoxy, N27-L-alanyl-L-alanyl), Cephabacin F; Cephaba E; 1'-Methanamine, O-de-Me, N. Ac, Caerulomycin E: cin F4, 28-Deoxy, Cephabacin F; Cephabacin F7, Cephaba 3-Methoxy, E-oxime, Caerulomycin E; E-Oxime, Caerulo cin F; Cephabacin F7, N27-L-Seryl, Cephabacin F; Cepha mycin E: Z-Oxime, Caerulomycin F, Caerulomycin F; bacin F7, N27-(L-Seryl-L-alanyl), Cephabacin H4. 3-Methoxy, Caerulomycin K, Caffeate 3,4-dioxygenase, Cal Cephabacin H4; 28-Deoxy, Cephabacin H4; 28-Deoxy, N27 cimycin; De?methylamino), 3-hydroxy, Calcimycin; L-alanyl, Cephabacin H4; 28-Deoxy, N27-(L-alanyl-L-ala 14-Demethyl, de(methylamino), Caldarchaeol; O-B-D-Ga nyl), Cephabacin H4; N27-L-Seryl, Cephabacin H4; N27-(L- lactofuranosyl-(1->6)-B-D-galactofuranoside. Caldar Seryl-L-alanyl), Cephabacin M; Cephabacin M1, chaeol; O-C-D-Glucopyranosyl-(1->2)-B-D-6-O-acetyl-3- CephabacinM; Cephabacin M2, CephabacinM; Cephabacin D-galactofuranoside. Caldarchaeol; O-C-D- M3, CephabacinM; Cephabacin M4, CephabacinM; Cepha Glucopyranosyl-(1->2)-B-D-galactofuranoside. bacin M5, CephabacinM; Cephabacin M6, Cephalosporin-C Caldarchaeol; O-C-D-Glucopyranosyl-(1->2)--D-galacto deacetylase, Cephalosporin C transaminase, Cerein B2, furanoside, O'-B-D-galactofuranoside, Caldarchaeol; O-(3- Cereins, Cereins; Cerein 7, Cereins; Cerein 8A, Cereins; O-Phosphoglyceryl), Caldarchaeol; O-(3-O-Phosphoglyc Cerein MRX1, Cereulide, Cereulide; Homologue eryl), O'-B-D-galactofuranosyl-(1->6)--D- (R-CH2CH3), Cerexins, Cervinomycin A1, Cervinomycin galactofuranoside. Caldarchaeol; O-(3-O- A1: 8,15-Quinone, Cervinomycin A1; 8,15-Quinone, O12 Phosphoglyceryl), O'-O-D-glucopyranosyl-(1->2)--D- de-Me, Chaetomacin, Chandrananimycin C, Chejuenolide A, galactofuranoside, Calditol, Calicheamicin, Camphor Chejuenolide A: 2-Epimer, Chinosporin S. Chitinovorin C, US 2016/01 86168 A1 Jun. 30, 2016

Chitinovorin D, Chitosanase, Chitovibrin, Chivosazole E, pheromone, ComXRO-B-2 pheromone, ComXRO-C-2 Chivosazole E. Aglycone, 20-Meether, Chivosazole E: 2,3'- pheromone, ComXRO-E-2 pheromone, ComXRO-H-1 Di-Meether, Chivosazole E: 6E-Isomer, 2',3',20-tri-Meether, pheromone, Coproporphyrinogen oxidase, Corallolysin, Chivosazole E: 20-Me ether, Chivosazole E: 3'-Me ether, Corallopyronin A, Corallopyronin B, Corallopyronin C, Cor Chivosazole E; 2',3'20-Tri-Meether, Chivotriene, Chloram mycin A, Coronafacic acid, Coronafacic acid; L-Alloisoleu phenicol: (1R,2R)-form, Chloramphenicol O-acetyltrans cine amide, Coronafacic acid; L-Isoleucine amide, ferase, Chlorate reductase, Chloridazon-catecholdehydroge Coronafacic acid; L-Serine amide, Coronafacic acid; nase, Chlorobactene, Chlorobactene; 1,2'-Dihydro, L-Threonine amide, Coronafacic acid; L-Valine amide, Coro 1'-hydroxy, Chlorobactene; 1,2'-Dihydro, 1'-hydroxy, O-(6- natine, Corpeptins, Corrin-aminopropanol-phosphoribose, dodecanoyl-f-D-glucopyranoside), Chlorobactene; 1,2-Di Corrugatin, Corrugatin: Homologue (R= hydro, 1'-hydroxy, O-B-D-glucopyranoside, 2-Chloroben CH2CH2CH2NH2), Corynicin JK, Corynomycolic acid: Zoate 1,2-dioxygenase, Chlorobiumquinone, 3-Chloro-4-(3- (2R,3R)-form, Corynomycolic acid; (2R,3R)-form, 11,12 chloro-2-nitrophenyl)-1,5-dihydro-5-methoxy-2H-pyrrol-2- Didehydro, Corynomycolic acid; (2R,3R)-form, 7",8,11,12 one: (-)-form, 4-Chloro-3-(3-chloro-2-nitrophenyl)-1,5- Tetradehydro, Creatinase, Creatininase, 4-Cresoldehydroge dihydro-5-methoxy-2H-pyrrol-2-one; (+)-form, 4-(2- aSC (hydroxylating), p-Cresolyldicyanocobamide, Chloroethyl)-2,6-dinitrophenol, 2-Chloro-3-(4-hydroxy-3,5- p-Cresolyldicyanocobamide: 4"-De-Me, Crisamicin A, dinitrophenyl)propanoic acid: (S)-form, 2-Chloro-3-(4- Crisamicin A; 4'a, 10'a-Epoxide, Crisamicin A; 1-Hydroxy, hydroxy-3-nitrophenyl)propanoic acid: (S)-form. 5-Chloro Crisamicin A; 9'-Hydroxy, Crispacin A, Crocacin A, Croca 6-methoxy-1-methyl-1H-indole-2,3-dione, 2-Chloro-1,6- cin A; N10-DeCaminoalkyl). Crocacin A; 5,6-Dihydro, Cro phenazinediol, 4-Chlorophenylacetate 3,4-dioxygenase, cacin A; Parent acid, Crossover junction endodeoxyribonu 2-(4-Chlorophenyl)ethylamine; N.N-Dichloro, Chlorophyll clease, Cruentaren A. Cruentaren B. Cry45Aa, a; 1"2"-Didehydro, Chlorophyll b: 1'2'-Didehydro, Chlo B-Cryptoxanthin; O-9-Methyldecanoyl-(->6)-B-D-glucopy ropolysporin B, Chloropolysporin B; Galactosyl, Chlo ranoside, B-Cryptoxanthin; O-11-Methyldodecanoyl-(->6) ropolysporin B; O-Derhamnosyl, 8-Chloro-7-propyl-4,7-oc B-D-glucopyranoside, B-Cryptoxanthin; O-13-Methyltet tadienoic acid; (4E.7E)-form, Chlorotetaine, Chlorotetaine; radecanoyl-(->6)-B-D-glucopyranoside, C-terminal Bromo analogue, Chlorothricin; 3B O-Deacyl, 4B O-(3- processing peptidase, Cucumopine, Cucumopine: 4-Epimer, chloro-6-methoxy-2-methylbenzoyl), Chlorotonil A, 4-Chlo Curvacin A, Curvalicins, Curvaticins, Curvaticins; Curvati rotryptophan: (S)-form, 5-Chlorotryptophan: (S)-form, cin 13, Curvaticins; Curvaticin FS47, Curvaticins; Curvaticin Chlortetracycline: 8-Methoxy, Cholestan-3-one: 5B-form, L442, Cutinase, CW 5, 3-Cyano-1-(3,5-dichlor-2-hydrox Cholest-5-en-3-ol: 3.3-form, O-(6-O-Hexadecanoyl-B-D-ga yphenyl)-1-propanone, Cyano-5-hydroxybenzimidazolylco lactopyranoside), Choline kinase, Choline Sulfatase, bamide, Cyano-5-hydroxybenzimidazolylcobamide; 5-Me Choloyl-CoA hydrolase, Chondramide A, Chondramide A: ether, N-1 -Cyano-2-(4-hydroxyphenyl)ethenylformamide: 2'-Chloro, Chondramide A: 2-Chloro, demethoxy, Chondra (Z)-form, Cyano-5-methoxy-6-methylbenzimidazolylcoba mide A: Demethoxy, Chondrochloren A, Chondrochloren A; mide, Cyano-5-methylbenzimidazolylcobamide, 3-Cyanom 2-O-De-Me, 2-Et ether, Chondro-4-sulfatase, Chondro-6- ethyl-3-hydroxyOXindole: (S)-form, Cyanophycinase, Cya Sulfatase, Chromoazepinone A: (S)-form, Chromoazepinone nuric acid amidohydrolase, Cyclic-(1->2)-B-D-glucans, A: (S)-form, N,4-Didehydro, Chromoazepinone C, Chro Cyclic-guanylate-specific phosphodiesterase, 2.3-Cyclic moviridan, Chromoviridan: Deoxy, Chryseomonin, Chryso nucleotide 2'-phosphodiesterase, Cyclo(alanyl-4-hydrox bactin, Chrysopine, ChuangXinmycin B, ChuangXinmycin C, yprolyl); (3S,7R,8aR)-form, Cyclo(alanyl-4-hydroxyprolyl); Cinerubin B: 5C-Epimer, Cinerubin B; 10-Epimer, (E)-Cin (3S,7R,8aS)-form, Cyclo(alanylisoleucyl); (1’S.3S,6S)- namoyl-CoA:(R)-phenylactate CoA-transferase, Circularin form, Cyclo(alanylisoleucylprolyleucyl), Cyclo(ala A, Circulocin C. Circulocin C: 3'-Deoxy, Circulocin Y. Cir nyleucyl); (3S,6S)-form, Cyclo(alanylprolyl); (3S,8aS)- culocin Ö, Citramalate CoA-transferase, Citrate CoA-trans form, Cyclo(arginylprolyl); (3S,8aR)-form, Cyclobrassinin, ferase, Citrate lyase deacetylase, Citrate lyase holo-acyl Cyclobrassinin; 5-Methoxy, 4,9-didehydro, Cyclocarbamide carrier-protein synthase, Citrate synthases; Citrate (Re)- A, Cyclocarbamide A: N-Hexanoyl analogue, C.-Cyclodex synthase, Citreamicin C. Citreamicin C.: O2-De-Me, trin, B-Cyclodextrin, Y-Cyclodextrin, Cyclo(glutamylglycyl Citreamicin f3, Citreamiciny, Citreamicin m, Citromycetin, prolyl), Cyclo(glutamylglycylserylprolyl), Cyclo(glutamyl Citrusnin A, Cittilin A, Clausin, Closthioamide, Closthioam prolylglutamylprolyl), Cyclo(glycylprolyl): (S)-form, 3.5- ide D. Closthioamide F, Closthioamide F: 3"-Carboxylic Cycloheptadien-1-ol. 2.4.6-Cycloheptatrien-1-one, acid, Closthioamide H, Closthioamide H. Nitrile, Closticin 10-Cycloheptyldecanoic acid, 13-Cycloheptyl-2-hydrox 574, Clostocins, Clostomicin C, Clostomicin D, Clostrham ytridecanoic acid, 11-Cycloheptyl-2-hydroxyundecanoic nan, Clostridial aminopeptidase, Clostripain, CM 101, CoA acid; (R)-form, 11-Cycloheptyl-4-methylundecanoic acid; disulfide reductase, Coagulin, Cob(II)alamin reductase, (S)-form, 9-Cycloheptylnonanoic acid, 13-Cycloheptyltride Cobalt-factor II C20-methyltransferase, Cob(I)yrinic acid canoic acid, 11-Cycloheptylundecanoic acid, Cyclohexane C.Y-diamide adenosyltransferase, Cob(II)yrinic acid a,c-dia 1.2-diol dehydrogenase, Cyclohexanol dehydrogenase, mide reductase, Cochinmicin I, Cochinmicin I; 5"-Chloro, Cyclohexanone monooxygenase, Cyclohexylamine oxidase, Cochinmicin I; 2-Epimer, Cochinmicin I; 2-Epimer, Cyclo(histidylproline); (S,S)-form, Cyclo(4-hydroy pro 5'-chloro, Cochinmicin I; 2-Epimer, 17-hydroxy, 5'-chloro, lyleucyl-4-hydroxyproyleucyl); (2R,2'S,2"S.2"S.4R,4"R)- Coenzyme B12, Coenzyme-B sulfoethylthiotransferase, form, Cyclo(4-hydroxyprolylphenylalanyl); (3S,7R,8aS)- Coenzyme Q: Coenzyme Q5, Coenzyme Q: Coenzyme Q8, form, Cyclo(4-hydroxyprolyltyrosyl); (3S,7R,8aR)-form, Coenzyme Q: Coenzyme Q9, Colicin E3, Colicins, Cyclo(4-hydroxyprolyltyrosyl); (3S,7R,8aS)-form, Cyclo(i- Coliformin, Colisan, Collagenase, Collagenase clostridium soleucyleucylisoleucyleucyl), Cyclo(isoleucylpipecolinyl); histolyticum, Columbicin A, CO-methylating acetyl-CoA (3R,9aR)-form, Cyclo(isoleucylprolyl); (1'S.3S.8aS)-form, synthase, Comirin, ComX168 pheromone, ComXRO-B-1 Cyclo(isoleucylprolyleucylprolyl); (all-L)-form, Cyclo(iso

US 2016/01 86168 A1 Jun. 30, 2016 30 cin E760, Enterocins: Enterocin EIA, Enterocins: Enterocin form, 2-(1-Ethylpentyl)-2,3-dihydro-4(1H)-quinazolinone; EJ97, Enterocins: Enterocin EL1, Enterocins: Enterocin (1R,2S)-form, 2-(1-Ethylpentyl)-2,3-dihydro-4(1H)- ESF100, Enterocins: Enterocin FH99, Enterocins: Enterocin quinazolinone: (1R,2S)-form, 1,2-Didehydro, 4-Ethyl-1H HF. Enterocins: Enterocin HJ35, Enterocins: Enterocin I, pyrrole-2-carboxaldehyde, Etnangiene, 11-Eudesmene-1,4- Enterocins: Enterocin IT, Enterocins: Enterocin 416K1, diol: (13.4C.)-form, Eurocidin C, Eurocidin D, Eurocidin D; Enterocins: Enterocin KP Enterocins: Enterocin L50, 7-Deoxy, Everninomicin A, Everninomicin A; 4A-O-De-Me, Enterocins: Enterocin LR76, Enterocins: Enterocin MC13, Everninomicin A; 3-Chloro, Everninomicin A; 3'-Dechloro, Enterocins: Enterocin 226NWC, Enterocins: Enterocin Everninomicin A; 3'-Dechloro, 2'-O-de-Me, Everninomicin ON-157, Enterocins: Enterocin P. Enterocins: Enterocin A; 2H.3H-De-O-methylene, 3H O-formyl, Everninomicin RJ-11, Enterocins: Enterocin S37, Enterocins: Enterocin B, Everninomicin B: 2D-Deoxy, Everninomicin C, Exodeox S760, Enterocins: Enterocin SD, Enterocins: Enterocin SE yribonuclease I, Exodeoxyribonuclease III, Exodeoxyribo K4. Enterocins: Enterocin U7, Enterocins: Enterocin UQ1, nuclease (lambda-induced), Exodeoxyribonuclease V. Enterocins: Enterocin V24, Enterocins: Enterocin W. Exodeoxyribonuclease VII, Exo-poly-O-galacturonosidase, Enterocins; Enterocin X, Enterococcins; Enterococcin A Exoribonuclease H, Exoribonuclease II, Exotoxin A, Factor 2000, Enterococcins: Enterococcin EFS2, Enterococcins; S1, Factor S3, FAD synthetase, Faktor I, Faktor III, Farnesyl Enterococcin V583, Enterocoliticin, Enterolysin A, Entero trans-transferase, Fatty acid synthase, Fengycin, Ferredoxin toxin, Entianin, Entolysin A, Entomocin 110, Entomocin reductases; Ferredoxin-NADP(+) reductase, Ferredoxin 420, Entomocin 9. EPF, Ephedrine dehydrogenase, Epicidin reductases; Ferredoxin-NAD(+) reductase, Ferribactin 18.1, 280, Epidermicin NI 01, Epidermin, Epidermin: 1-Valine Ferribactin G173, Ferribactin G173; NGlu-Ac, Ferribactin 6-leucine analogue, Epilancin K7, Epilancin 15X. Epothilone G173; NGlu-Di-Ac, Ferribactin G173; NGlu-Hydroxy, Fer A, Epothilone A: 3-O-C-D-Arabinofuranoside, Epothilone ribactin PS 6.10-A, Ferricrocin, Ferrioxamine D2, Ferrocin, A; 8-Demethyl 3-O-O-D-arabinofuranoside, Epothilone A: Ferroxidase; Rusticyanin, Feruloyl esterase, FIC, Figarolinic 21-Hydroxy, Epothilone A: 27-Hydroxy, Epothilone A; Par acid, Fijiolide A, Fijiolide A: N-De-Ac, Fla-P3, Fla-P3; ent hydroxyacid, Epothilone A; Parent hydroxyacid, Me 3-Chloro, Fla-P4, Fla-P4; 3-Chloro, Fla-P5, Flavocin, Flavo ester, Epothilone A1, Epothilone A1: 4-Epimer, Epothilone lipids, Flavotoxin A. Flazine, Flexirubin, Flexirubin; A8, Epothilone B, Epothilone B: 3-O-O-D-Arabinofurano 5-Chloro, Flexixanthin, Flexixanthin; 3-Deoxy, Flexixan side. Epothilone B: 21-Hydroxy, Epothilone B: 21-Methyl, thin; 3-Deoxy, O-3-D-glucopyranoside, Flexixanthin; Epothilone C, Epothilone C: 3-O-C-D-Arabinofuranoside, 3-Deoxy. 2R-hydroxy, Flexixanthin; 3-Deoxy, 25-hydroxy, Epothilone C; 16-Demethyl, Epothilone C. 4-Demethyl, Flexixanthin; 3-Deoxy, O-11-methyldodecanoyl-(->6)-B- 9-oxo, Epothilone C; 10, 11-Didehydro(E-), Epothilone C: D-glucopyranoside. Flexixanthin; 2'S-Hydroxy, Flexixan 8.9-Didehydro(E-), Epothilone C; 14C.-Hydroxy, Epothilone thin; 2'-Hydroxy, 1,3-di-Me ether, Flexixanthin; 2'S-Hy C; 27-Hydroxy, Epothilone C; 27-Hydroxy, 3-O-O-D-ara droxy, 1'-O-B-D-xylopyranoside, Flexixanthin; 2'S- binofuranoside, Epothilone C1, Epothilone C1: 4-Epimer, Methoxy, Flexixanthin; 2-Methoxy, 1,3-di-Me ether, Epothilone C1: 4-Epimer, 12E-isomer, Epothilone C1; 12E Fluopsin B, Fluopsin C, Fluopsin N, 9-Fluorenol dehydroge Isomer, Epothilone C3, Epothilone C4, Epothilone D. nase, Fluvibactin, Fluviol D, Fluvirucin A; Fluvirucin A1, Epothilone D: 4-Demethyl, 10,11-didehydro(E-), Epothilone Fluvirucin A; Fluvirucin A1,3'-N-Me, Fluvirucin A; Fluviru D; 6-Demethyl, 10,11-didehydro(E-), Epothilone D: 4-Dem cin A1, 6-Demethyl, 3'-N-Me, Fluvirucin A; Fluvirucin A2, ethyl, 9-oxo, stereoisomer 1, Epothilone D: 4-Demethyl, Fluvirucin B: Fluvirucin B0, Fluvirucin B: Fluvirucin B3, 9-oxo, stereoisomer 2, Epothilone D; 10.11-Didehydro(E-), 4'-Epimer, 2'-O-B-D-glucopyranosyl-(1->4)-O-D-glucopy Epothilone D; 8.9-Didehydro(E-), Epothilone D; 8-Epimer, ranosyl, Fluvirucin B; Fluvirucin B3, 4'-Epimer, N3'-2-(2- 9-oxo, Epothilone D; A1112-Isomer, 9-oxo, Epothilone D; phenylethyl)aminocarbonyl, Fluvirucin B; Fluvirucin B3, 9-Oxo, Epothilone D; 9-Oxo, 10,11-didehydro(E-), N3'-2-(2-Phenylethyl)aminocarbonyl, Fluvomycin, For Epothilone D1, Epothilone D1: 4-Epimer, Epothilone H1, madicins, Formaldehyde dehydrogenases; Formaldehyde Epothilone H1; 12C., 13C-Epoxide, Epothilone H2, dehydrogenase, Formate-C-acetyltransferase-activating Epothilone H2; 12C., 13C-Epoxide, Epothilone I1, Epothilone enzyme, Formate C-acetyltransferase, Formate dehydroge I2, Epothilone I3, Epothilone I4, Epothilone I5, Epothilone nases; Formate dehydrogenase (cytochrome-553), Formate I5: 4-Epimer, Epothilone K, Epothilone M, Epothilone N. dehydrogenases; Formate dehydrogenase (NADP(+)). For Epothilone tetrahydrofuran, Epoxomicin, 13,17-Epoxy-16 mate kinase, Formimidoylaspartate deiminase, Formim hydroxymacrolactin A, 15,17-Epoxy-16-hydroxymacrolac idoylglutamase. Formimidoylglutamate deiminase, Formyl tin A, 13.14-Epoxy-15-oxohexadecanoic acid, trans-Ep CoA hydrolase, Formyl-CoA transferase, oxysuccinate hydrolase, 9,11-Eremophiladiene-1,3-diol; Formylmethanofurantetrahydromethanopterin N-formyl (13.3C.,4C,5B)-form, Ericin A, Erwinicin, Erythrazole A, transferase, 5-(Formyloxymethyl)uridine, 5-Formyl-1H-pyr Erythrazole B, Erythritol kinase, Erythromycin, Esein, Espe role-2-carboxylic acid, Fortimicin AH, Fortimicin AH; rin, Ethane, 1.2-Ethanediol. 2,2'-(1.2-Ethanediyl)bis 1-me 3-Epimer, Fortimicin AK. Fortimicin AO, Fortimicin B, thyl-3-piperidinone; (RSSR)-form, Ethanolamine kinase, Fortimicin B: 1-N-(Aminoacetyl), Fortimicin B: 1-N-(Ami Ethanolamine oxidase, Ethoxyacetic acid, Ethylamine, Eth nocarbonylamino)acetyl. Fortimicin B; O-De-Me. 1-N- ylbenzene hydroxylase, 3-(2-Ethyl-2-butenyl)-9,10-dihydro (aminoacetyl), Fortimicin B; O-De-Me, 4-N-(aminoacetyl), 1.6.8-trihydroxy-9,10-dioxo-2-anthracenecarboxylic acid, Fortimicin B; O-De-Me, 1-N-(aminocarbony)amino 2-Ethyl-1,8-dihydroxy-3-methylanthraquinone, 2-Ethyl-1.8- acetyl. Fortimicin B; 1,6-Diepimer, Fortimicin B; 1.6- dihydroxy-3-methylanthraquinone; 8-Me ether, 1-(4-Ethyl Diepimer, O-de-Me, Fortimicin B; 2,5-Diepimer, 1-N- 3,5-dihydroxyphenyl)-2-phenylethylene; (E)-form, 3-Ethyl (formylamino)acetyl. Fortimicin B; 6-Epimer, Fortimicin 2,5-dimethylpyrazine, 2-Ethylmalate synthase, B: 6-Epimer, 2-N-(aminoacetyl), Fortimicin B: 1-Epimer, 3-Ethylmalate synthase, 2-Ethyl-4-methylcuinazoline, 2-(1- O-de-Me, Fortimicin B: 1-N-(Formylaminoacetyl). Fortimi Ethylpentyl)-2,3-dihydro-4(1H)-quinazolinone: (1R,2R)- cin B: 1-N-(2-Hydroxyethyl), Fortimicin B: 1-N-(Iminom

US 2016/01 86168 A1 Jun. 30, 2016 36 proteins; Rubredoxin, IS, Isoamylase, Isoapoptolidin A, Kutzneride 1: 3-Epimer, 4"R-chloro, Kutzneride 1: Isoapoptolidin A; 6-Demethyl, Isobutyraldoxime O-methyl 3'-Epimer, 2",3"-didehydro, Kutzneride 1: 3'-Epimer, 4"R- transferase, Isochorismatase, Isocitrate dehydrogenase hydroxy. 2".3"-didehydro, Kyanomycin, Kynurenine 7,8- (NADP(+)) kinase, 3-(2-Isocyanoethenyl)-1H-indole: (Z)- hydroxylase, L 654040, Lacidin A, Lactacins, Lactacins; form, 4-(2-Isocyanoethenyl)phenol; (5)-form, O-O-L-Rham Lactacin B. Lactacins; Lactacin F, 3-Lactamase, Lactate nopyranoside, Isoglutamine; (R)-form, Isohematinic acid; dehydrogenases; D-Lactate dehydrogenase (cytochrome (+)-form, Isokibdelone A, Isokibdelone A; 6,7-Dihydro, c-553), Lactate 2-monooxygenase, D-Lactate-2-sulfatase, Isokibdelone A: 11-O-O-Rhamnopyranoside, Isoleucylpro Lacticins; Lacticin 3147, Lacticins; Lacticin 481, Lacticins; lylisoleucine; L-L-L-form, Isomaltotriulose, Isoneoantimy Lacticin BH5. Lacticins; Lacticin Q, Lacticins; Lacticin Z. cin, 8(14), 15-Isopimaradiene-2.3.18-triol: (2O.3?)-form, Lactivicin, Lactobacillus polypeptide 2. Lacto-N-biosidase, 2-Ketone, 2-Isopropenyl-5-isopropylpyrazine, 2-Isoprope Lactobrevin, Lactocepin, Lactocins, Lactocins; Lactocin nyl-6-isopropylpyrazine, 2-Isopropylmalate synthase, 2-Iso 160, Lactocins; Lactocin 27, Lactocins; Lactocin 705, Lac propyl-3-methoxy-5-(1-methylpropyl)pyrazine, 2-Isopro tocins; Lactocin A1, Lactocins; Lactocin C183, Lactocins; pyl-3-methoxy-5-(2-methylpropyl)pyrazine, 3-Isopropyl-6- Lactocin D. Lactocins; Lactocin LC-09, Lactocins; Lactocin methylene-2.5-piperazinedione: (S)-form, 2-Isopropyl-5-(1- P 109, Lactocins; Lactocin S. Lactococcin, Lactococcin: Lac methylpropyl)pyrazine, 2-Isopropyl-5-(2-methylpropyl) tococcin 140, Lactococcin: Lactococcin 972, Lactococcin; pyrazine, 2-Isopropyl-5-methylpyrazine, 2-Isopropyl-6- Lactococcin A, Lactococcin: Lactococcin B. Lactococcin; methylpyrazine, Isopropylpyrazine, Isopullulanase, Lactococcin BZ. Lactococcin; Lactococcin D53, Lactococ Isopyoverdin Pp BTP 1, Isopyoverdin Pp. CFML 90-33, cin, Lactococcin G. Lactococcin: Lactococcin K. Lactococ Isopyoverdin Pp CFML 90-44, Isoquinocycline A, Iso cin, Lactococcin K3113, Lactococcin; Lactococcin M. Lac quinocycline A; 2'-Epimer, 1"-ketone, Isoquinocycline A. tococcin; Lactococcin MMFII, Lactococcin; Lactococcin 1"-Ketone, 1-Isoquinolinecarboxylic acid; Nitrile, Isozeax MMT24, Lactococcin; Lactococcin Q, Lactococcin; Lacto anthin; Diketone, Iturin A, Iturin AL, Iturin D, Iturin E, Ize coccin R. Lactocyclicin Q, Lactolin, 1.4-Lactonase, Lac namicin B2, IZenamicin B2, Aglycone, IZenamicin B2; tostrepcins, Lactulosucrose, Lanthiopeptin, Lariatin A, Lari 23-Deoxy, 13C, 14C-epoxide, Izumenolide, Izumenolide; atin B. Laterocidin, Laterosporamine, Laterosporin, 38.39-Dihydro, 39-sulfooxy, Izumenolide: 2,3,38,39-Tet Latosillan, Lebstatin: 17-O-De-Me, Legiobactin, Lemon rahydro, 39-sulfooxy, Janthinocin B, Janthinocin B; nierin, Leprotene, Leprotene; 3,3'-Dihydroxy, Leprotene: B-Deoxy, Janthinocin B: C.B-Dihydro, Jawsamycin, JBIR 78, 3-Hydroxy, Leucine dehydrogenase, Leucocidin R1, Leu JBIR95, Jegathesan, Jenseniin G, Jenseniin P. Jerangolide A, cocins; Leucocin 4010, Leucocins; Leucocin A, Leucocins: Jerangolide A: 18-Deoxy, Jerangolide A: 18-Deoxy, 13,145 Leucocin B, Leucocins; Leucocin B-TA33b, Leucocins; Leu dihydro, Jerangolide A: 18-Deoxy, 13,145-dihydro, 145-hy cocin C. Leucocins; Leucocin D LaS4a, Leucocins; Leucocin droxy, Jerangolide A; 13,145-Dihydro, Jolipeptin, Juglone F10, Leucocins; Leucocin H. Leucocins; Leucocin K, Leu 3-monooxygenase, Juvenimicin B1, Juvenimicin B1; 20-A1 cocins; Leucocin N. Leucocins; Leucocin OZ, Leucocins; dehyde, Juvenimicin B1; 20-Carboxylic acid, 12S,13S-ep Leucocin Q. Leucocyclicin Q. Leucylisoleucylargininal; oxide, Juvenimicin B1; 20-Deoxy, Juvenimicin B1; N—Ac, Leucyltransferase, Leucylvalylargininal; N-Ac, 20-Deoxy, 12S,13S-epoxide, Juvenimicin B1; 12S,13S-Ep Leuhistin, Leupyrrin C. Leupyrrin C; 2',3-Didehydro, oxide, Juvenimicin B1; 23-Hydroxy, Juvenimicin B1; 23-Hy Leupyrrin C; 19.20-Didehydro, 21-Me ether, Leupyrrin C: droxy. 20-aldehyde, Juvenimicin B2, Juvenimicin B4, K13, 2',3'-Didehydro, 21-Me ether, Leupyrrin C; 21-Me ether, K7/3, Kailuin; Kailuin E, Kalimantacin A, Kalimantacin A; Leupyrrin C; 2',3'19.20-Tetradehydro, 21-Meether, Levan, 175-Alcohol, Kalimantacin A; 175-Alcohol, decarbamoyl, Levansucrase, Levantilide A, Levantilide A: 23-Ketone, Kalimantacin A; Decarbamoyl, Kalimantacin A; 10E-Isomer, Lichenicidin, Lichenicidin VK21, LicheniforminA, Licheni Kalimantacin C, Kanagawamicin, Kanamycin A; 3"-N-Me, formin B. Licheniformin C. Lichenin, Licheninase, Kanamycin B; 6"-O-Carbamoyl, Kanamycin B; 3',4'- Lichenysin A. Lichenysin G, Licoagroisoflavone; (R)-form, Dideoxy, 3",6'-N,N-di-Me, Kanamycin B; 3',4'-Dideoxy, Lignostilbene C.B-dioxygenase, Limazepine B1, Limazepine 3"-N-Me, Kanamycin B; 3"-N-Me, Kanamycin kinase, B1; 11-Deoxy, 10,11-didehydro, Limazepine B1; 11-Deoxy, Kanglemycin C, 6a, 12a-Didehydro, Karalicin, Katanosin A, 1,10,11,11a-tetradehydro, Limazepine B1; 11-Epimer, Katanosin B, Kayamycin, Kedarcidin, Kefiran, Kenyacin Limazepine B1: A2,12-Isomer, 11-deoxy, 10,11-didehydro, 404, Keratan-sulfate endo-1,4-B-galactosidase, Kibdelomy Limazepine B1; 11-Ketone, Limazepine F. Limnazine, cin, Kibdelone A, Kibdelone A; 6,7-Dihydro, Kibdelone A: Limonene-1,2-epoxide hydrolase, Limonin-D-ring-lacto 6,7-Dihydro, 12-O-O-L-rhamnopyranoside, Kibdelone A: nase, Linalool 8-monooxygenase, Lincomycin, Linecin A, 5,16-Hydroquinone, 6,7-dihydro, Kibdelone A; 5,16-Hydro Linenscin OC2, Linnoculicin 819, Lipiarmycin A; Lipiarmy quinone, 6,7-dihydro, 12-O-O-L-rhamnopyranoside, Kibde cin A3, Lipiarmycin A; Lipiarmycin A3, 4B-Deacyl, 3B-(2- lone A, 10-Ketone, Kibdelone A, 12-O-O-L-Rhamnopyrano methylpropanoyl), Lipiarmycin A; Lipiarmycin A3. side, Kistamicin A, Kistamicin B, Klebicins, Klebocin, 4B-Deacyl, 2B-(2-methylpropanoyl), Lipiarmycin A; Lipiar Bacillus pumilus KMM 1364 Lipodepsipeptides, Bacillus mycin A3. 4B-Deacyl, 2B-propanoyl, Lipiarmycin A; Lipi subtilis KMM 457 Peptide 1, Bacillus subtilis KMM 457 armycin A3, 20-De?glycosyloxy), 18-deoxy. 4B-deacyl, Peptide 2, Kojibiose phosphorylase, Kojic acid dimer, Koji 4B Ac, Lipiarmycin A; Lipiarmycin A3, 3A-Aroyl isomer, hexaose, Kojitriose, Kokandomycin, Korkormicins, Koror 4A,4B-dideacyl, 2B-(2-methylpropanoyl), Lipiarmycin A; micin A, Korormicin B, Korormicin C, Korormicin D, Kris Lipiarmycin A3... 3"-Dechloro, Lipiarmycin A; Lipiarmycin tenin, Kudzuisoflavone A: 5.5"-Dihydroxy, Kudzuisoflavone A3, Didechloro, Lipiarmycin A; Lipiarmycin A3, 18-Deoxy, A: 5-Hydroxy, Kurstacin 287, Kurstakins, Kusaya antibiotic, Lipiarmycin A; Lipiarmycin A3, 18-Deoxy, 4B-deacyl, Lipi Kutzneride 1, Kutzneride 1: 4"R-Chloro, Kutzneride 1: 3"- armycin A; Lipiarmycin A3, 18-Deoxy, 11-deglycosyl, Lipi Demethyl, Kutzneride 1: 3"-Demethyl, 3'-epimer, armycin A; Lipiarmycin A3, 18-Deoxy, 11-deglycosyl, Kutzneride 1: 2",3"-Didehydro, Kutzneride 1: 3'-Epimer, 2A-O-de-Me, Lipiarmycin A; Lipiarmycin A3, 11-Deglyco US 2016/01 86168 A1 Jun. 30, 2016 37

Syl, 11-O-2-methylpropanoyl-(->4)-O-L-rhamnopyrano M; 7-O-B-D-Glucopyranoside, Macrolactin U, Macrollide side, Lipiarmycin A; Lipiarmycin A3, 18-Deoxy, 20-degly 2'-kinase, Madumycin II, Madumycin II; 13-Deoxy, Madu cosyl, Lipiarmycin A; Lipiarmycin A3, 18-Deoxy, rahydroxylactone, Madurahydroxylactone; 3-O-Butyl, Mag 20-deglycosyl, 4B-deacyl, Lipiarmycin A; Lipiarmycin A3. nesidin, Magnesium-protoporphyrin IX methyltransferase, 18-Deoxy, 20-deglycosyl, 4B-deacyl, 4B Ac, Lipiarmycin Maklamicin, Malate synthase, Malonate CoA-transferase, A; Lipiarmycin A3, 18-Deoxy. 20-deglycosyl, 4B-deacyl, Maltophilin, Maltophilin; 20O.-Alcohol, Maltophilin; Stere 4B-propanoyl, Lipiarmycin A Lipiarmycin A3, 18-Deoxy, oisomer, Maltose O-acetyltransferase, Maltose-6-phosphate 11.20-dideglycosyl, Lipiarmycin A; Lipiarmycin A3. glucosidase, Maltose phosphorylase, Mandelate 4-monooxy 18-Deoxy, 11.20-dideglycosyl, 20-O-B-D-mannopyrano genase, Manilosporin, Mannan endo-1,6-O-mannosidase, side, Lipiarmycin A; Lipiarmycin A3, 20-De(glycosyloxy), Mannan exo-1,2-1,6-O-mannosidase, Mannan 1,4-manno 18-deoxy, 11-deglycosyl, Lipiarmycin A; Lipiarmycin A3. biosidase, Mannan 1.2-(1,3)-O-mannosidase, Mannan endo 20-De?glycosyloxy), 18-deoxy, Lipiarmycin A Lipiarmycin 1,4-B-mannosidase, Mannokinase, B-D-Mannopyranosyl A3, 20-De?glycosyloxy), 18-deoxy. 4B-deacyl, Lipiarmycin (1->4)-C-D-galactopyranosyl-(1->4)-L-rhamnose, 3-O-O- A; Lipiarmycin A3, 20-De?glycosyloxy), 18-deoxy, D-Mannopyranosyl-D-glucose, 2-O-O-D-Mannopyranosyl 4B-deacyl, 4B-propanoyl, Lipiarmycin A; Lipiarmycin A3. myo-inositol: 1-Pentadecanoyl, 6'-heptadecanoyl, C-D- 20-De?glycosyloxy), 18-deoxy, 18-methyl, Lipiarmycin A; Mannopyranosyl-(1->2)-O-D-mannopyranosyl-(1->3)-D- Lipiarmycin A4, 4B-Deacyl, 2B-(2-methylpropanoyl), Por galactose, 3-D-Mannopyranosyl-(1->2)-C-D- phyromonas gingivalis 381 Lipid A. Lipid A disaccharide mannopyranosyl-(1->2)-D-mannose, B-D-Mannopyranosyl synthase, Lipid X, Lipid X: 3'-O-Hexadecanoyl, Lipoate pro (1->4)-C-D-mannopyranosyl-(1->3)-L-rhamnose; tein ligase, Shewanella pacifica Lipooligosaccharide, C.-Pyranose-form, 3'-Ac, C.-D-Mannopyranosyl-(1->4)-O-L- Lipopolysaccharide N-acetylglucosaminyltransferase, rhamnopyranosyl-(1->3)-D-galactose, B-D-Mannopyrano Lipopolysaccharide N-acetylmannosaminouronosyl syl-(1->4)-O-L-rhamnopyranosyl-(1->3)-D-galactose, B-D- transferase. Lipopolysaccharide 3-O-galactosyltransferase, Mannopyranosyl-(1->2)-O-L-rhamnopyranosyl-(1->4)-L- Lipopolysaccharide glucosyltransferases; Lipopolysaccha rhamnose, 4-O-O-D-Mannopyranosyl-L-rhamnose 4-O-B- ride glucosyltransferase I, lipopolysaccharide glucosyltrans D-Mannopyranosyl-L-rhamnose, B-D- ferases; Lipopolysaccharide glucosyltransferase II, Lipoyl Mannopyranuronosyl-(1->4)-B-D-glucopyranosyl-(1->4)- synthase, LIQ 4, Littorine; N-De-Me, Littorine; 3'-Hydroxy, D-galactose, 4-O-B-D-Mannopyranuronosyl-D-glucose, Lobatamide A: Stereoisomer (?), Loihichelins, Loloatins: Mannose 1-phosphate guanylyltransferase, Mannose 1-phos Loloatin A, Loloatins; Loloatin B. Loloatins; Loloatin C, phate guanylyltransferase (GDP), C-Mannosidase, B-Man LomaiviticinA, Lomaiviticin B, Long-chain-alcohol O-fatty nosidase, Mannosyl glycoprotein endo-B-N-acetylglu acyltransferase, LTA T. Lucentamycin B. Lumichrome, cosaminidase, Mannosyl-oligosaccharide 1.2-O- Lumichrome; N1-Me, Lumichrome; N1-C-Ribofuranosyl, mannosidase, Mannosyl-3-phosphoglycerate phosphatase, Luminamicin, Lupinacidin A, Lupinacidin B. Lupinacidin C, Mannosyl 3-phosphoglycerate synthase, Maracen A. Mara Lutein, Lutoside, Lycogalic acid, 20-Lycopenal: (13Z)-form, cin A, Marcellomycin, Marcellomycin; N-De-Me, Marcello Lycopene; (all-E)-form, 3,4-Didehydro(E-), 5',6'-dihydro, mycin; 10-Epimer, Marcescin, Maribasin A, Maribasin B, Lycophyll, Lyngbyatoxin A. N-De-Me, Lyngbyatoxin A; Maricin, Marihysin A, Marinobactins, Marinocine, Marin 19-Epimer, Lyngbyatoxin A; Meether, Lysidine, Lysine car olic acid A, Marinolic acid A., 8-Amide, Marinolic acid A4, boxypeptidase, Lysine dehydrogenases; Lysine 6-dehydroge Marinolic acid A6, Marinoquinoline F. Mannostatin, Masse nase, Lysine monooxygenases: Lysine 2-monooxygenase, tolides, Massetolides; Massetolide A, Diastereoisomer, Mas Lysine monooxygenases; Lysine 6-monooxygenase setolides; Massetolide C, Diastereoisomer, Matrucin; Matru (NADPH), Lysine transaminases; L-Lysine 6-transaminase, cin 1, Matrucin; Matrucin 2, Maytansinol: 3-Butanoyl, Lysinomycin, Lysostaphin, Lysyl endopeptidase, N1-(N-Ly Maytansinol; Dechloro, 4.5-deepoxy. 4,5-didehydro, N-de Sylphenylalanyl)cycloornithylvalyl, Lysyltransferase, LyXu Me, Maytansinol; 4.5-Deepoxy, 4.5-didehydro, N-de-Me, ronic acid; D-form, Maackiain, (-)-form, O-B-Glucopyrano Maytansinol; 4.5-Deepoxy. 4E,5-didehydro, N-de-Me, 3-O- side, Macbecin II: O11-De-Me, Macbecin II: O12-De-Me, (2-methylpropanoyl), Maytansinol; 4.5-Deepoxy, 4.5-dide Macbecin II: O15-De-Me, Macbecin II; 18.21-Quinone, hydro, O9-Me, N-de-Me, Maytansinol; N-De-Me, 3-Ac, O11-de-Me, Macbecin II; 18.21-Quinone, O12-de-Me, Maytansinol; N22-De-Me, 3-Ac, N22-B-D-glucopyranosyl, Macbecin II; 18.21-Quinone, O15-de-Me, Macedocin, Maytansinol; N-De-Me, 3-O-(3-methylbutanoyl), Maytansi Macedocin ST91 KM, Macquarimicin A, Macquarimicin B, nol; N-De-Me, 3-O-(2-methylpropanoyl), Maytansinol: Macquarimicin C, Macrolactin A, Macrolactin A; 7-Deoxy, N22-De-Me, 3-O-propanoyl, N22-(4-O-carbamoyl-B-D-glu 8,9-dihydro, 7,8-didehydro(E-), 9-hydroxy, Macrolactin A; copyranosyl), Maytansinol; 15R-Hydroxy, Maytansinol: 13-Deoxy, 16,17-dihydro, 15-ketone, Macrolactin A; 16,17 15R-Hydroxy, 3-Ac, Maytansinol: 30-Hydroxy, 3-Ac, May Dihydro, 15-ketone, 7-O-(3-carboxypropanoyl), Macrolactin tansinol; 15R-Hydroxy, 3-O-(3-methylbutanoyl), Maytansi A: 16,17-Dihydro, 15-ketone, 7-O-B-D-glucopyranoside, nol: 30-Hydroxy, 3-O-(3-methylbutanoyl), Maytansinol: Macrolactin A; 18S, 19S-Epoxide, Macrolactin A; 7-O-B-D- 3-O-(3-Hydroxy-3-methylbutanoyl), Maytansinol: 3-O-(4- Glucopyranoside, Macrolactin A; 7-O-(4-B-D-Glucopyrano Hydroxy-3-methylbutanoyl), Maytansinol: 3-O-(3-Hy sylsuccinoyl), Macrolactin A; 12S-Hydroxy, Macrolactin A; droxy-3-methylbutanoyl), N-de-Me, Maytansinol; 15R-Hy 20R-Hydroxy, Macrolactin A; 10E-Isomer, Macrolactin A; droxy, 3-O-(2-methylpropanoyl), Maytansinol; 15R 18Z-Isomer, Macrolactin A; 10E-Isomer, 16,17-dihydro, Hydroxy, 3-propanoyl, Maytansinol: 30-Hydroxy, 15-ketone, Macrolactin A; 10E-Isomer, 7-O-B-D-glucopyra 3-propanoyl, Maytansinol: 3-O-(3-Methylbutanoyl), May noside, Macrolactin A; 18Z-Isomer, 7-O-B-D-glucopyrano tansinol: 3-O-(2-Methylpropanoyl), Maytansinol: 3-Pro side, Macrolactin A; 7-Malonyl, Macrolactin A; 7-Succinoyl, panoyl, Mechercharstatin A, Mechercharstatin B. Mediola Macrolactin A; 7-O-(6-O-Succinoyl-B-D-glucopyranoside), cin, Megacins, Megacins; Megacin A19213, Megacins; Macrolactin H, Macrolactin L, Macrolactin M, Macrolactin Megacin Cx, Megacins; Megacin FW337, Megalomicin A,

US 2016/01 86168 A1 Jun. 30, 2016 39 lidinehexanoic acid; (4R,5S)-form, Methylpendolmycin, Mutacins; Mutacin F-59.1, Mutacins; Mutacin GS5, Mut 14-Methylpentadecanoic acid, 14-Methyl-5-pentadecenoic acins; Mutacin I, Mutacins; Mutacin II, Mutacins; Mutacin acid; (Z)-form, 3-Methyl-2-pentyl-4(1H)quinolinone, 9-Me III, Mutacins; Mutacin IV. Mutacins; Mutacin K8, Mutacins; thyl-1-phenyl-1-decanone, 3-Methyl-2,5-piperazinedione: Mutacin MT6223, Mutacins; MutacinN, Mutacins; Mutacin (+)-form, 2-Methyl-1,2-propanedithiol, 2-Methyl-1-propy VSM43, Mutamicin 5, Mutanobactin A, Mutanobactin A; lamine; N-Propyl, 3-(2-Methylpropyl)-2,5-piperazinedione: 25-Epimer, Mutanobactin A; 15-Li-Isoleucine analogue, (S)-form, 4-(2-Methylpropyl)-3H-pyrrolo2.3-cquinoline, Mutanobactin D. Mycinamycin II, Mycinamycin II; 3B O Methylpyrazine, 4-Methyl-3H-pyrrolo2.3-cquinoline, De-Me, Mycinamycin II: 14-Deoxy, Mycinamycin II; 4-Methylguinazoline, 4-Methyl-2-quinazolinecarboxylic 14-Deoxy, 3B O-de-Me, Mycinamycin II; 14-Deoxy, acid, 4-Methyl-2-quinazolinecarboxylic acid; Amide, 21-O-deglycosyl, Mycinamycin VI, Mycinamycin VI: Agly 12-Methyltetradecanoic acid; (5)-form, 12-Methyltetrade cone, Mycinamycin VI: Aglycone, 21-deoxy, Mycinamycin canoic acid: (S)-form, 2-Methyl-4-tetradecanone, 12-Me VI: 95-Alcohol. 2",3"-di-Meether, Mycinamycin VI; 21-O- thyl-4-tetradecenoic acid; (Z)-form, 13-Methyl-4-tetrade Deglycosyl, Mycinamycin VI, 21-(Deglycosyloxy), Mycina cenoic acid; (Z)-form, mycin VI: 2",3"-Di-Meether, Mycinamycin VI; 14C-Hy 5-Methyltetrahydropteroyltriglutamate-homocysteine S-me droxy, Mycinamycin VI; 14C-Hydroxy. 2",3'-di-Meether, thyltransferase, 3-Methyl-29-(2,3,4,5-tetrahydroxypentyl)- Mycinamycin VI; 14C-Hydroxy. 2"-Meether, Mycinamycin 6,11-hopadiene; (3.B.32R,33R,34R)-form,3-Methyl-29-(2,3, VI: 2"-Me ether, Mycinamycin XI, Mycinamycin XI; 4,5-tetrahydroxypentyl)-6,11-hopadiene: (3 B,32R,33R, 14-Deoxy, Mycinamycin XI; 11-Epimer, Mycinamycin XI; 34S)-form, 3-Methyl-29-(2,3,4,5-tetrahydroxypentyl) 11-Epimer, 14-deoxy, Mycinamycin XII, Mycinamycin XIII, hopane; (3,3,32R,33R,34R)-form, 3-Methyl-29-(2,3,4,5- Mycinamycin XIV. Mycinamycin XVII, Mycobacillin, tetrahydroxypentyl)hopane; (3.B.32R,33R,34S)-form, Mycobactocidin, Mycocerein, Mycodextranase, Mycoheptin 3-Methyl-29-(2,3,4,5-tetrahydroxypentyl)-11-hopene; (3,3, B. Mycopentene, Mycoplanecin, Mycoplasmal growth 32R,33R,34R)-form, 3-Methyl-29-(2,3,4,5-tetrahydroxy inhibitor, Mycosubtilin, Mycosubtilin B. Mycosubtilin C, pentyl)-11-hopene; (3f.32R,33R,34S)-form, 3-Methyl-29 Mycothiol bimane, Mycotrienol II; 20.23-Quinone, 19-hy (2,3,4,5-tetrahydroxypentyl)-6-hopene; (3 B.32R,33R.34S)- droxy, 13-O-2-(cyclohexanecarbonyl)aminopropanoyl. form, Methylthioadenosine nucleosidase, 1-(Methylthio) Myomycin B, Myxalamides; Myxalamide A, Myxalamides: butane: S.S.-Dioxide, 3-(Methylthio)propanoic acid, Myxalamide B. Myxalamides; Myxalamide C, Myxala S-Methyl-5-thioribose kinase, 3-(Methylthio)rifamycin, mides; Myxalamide D, Myxalamides; Myxalamide D, 2-Me 3-(Methylthio)rifamycin; 16, 17,18,19,28.29-Hexahydro, ether, Myxalamides; Myxalamide D, 6E-Isomer, 7-Meether, 3-(Methylthio)rifamycin; 1,4-Quinone, 3-(Methylthio)rifa Myxalamides; Myxalamide D, 6E, 10Z-Isomer, 2-Me ether, mycin; 1,4-Quinone, 16, 17, 18, 19.28.29-hexahydro, 2-Me Myxaline, Myxochelin A, Myxochelin A; 10-Deoxy, thyl-4-tridecanone, 3-Methyl-4-tridecanone; (5)-form, 10-amino, Myxochelin A; 10-Deoxy, 10-(2,3-dihydroxyben 2-Methyl-2-tridecen-4-one, Methylumbelliferyl-acetate Zoylamino), Myxochromide A, Myxochromide B, Myxo deacetylase, 10-Methylundecanoic acid, 10-Methyl-2-unde chromide S, Myxocoxanthin, Myxocoxanthin; O-B-D-Glu canol; (5)-form, 10-Methyl-2-undecanone, 3-O-Methylxy copyranoside, Myxocoxanthin; Me ether, Myxocoxanthin; lose; L-form, 1'-Methylzeatin; (R)-form, 1'-Methylzeatin: O-O-L-Rhamnopyranoside, Myxol, Myxopyronines: Myx (R)-form, 9-3-D-Ribofuranosyl, Met-Xaa dipeptidase, Mev opyronine A, Myxopyronines; Myxopyronine B, Myxothia alagmapeptide, Mevalonate kinase, MGCI, Micacocidins; Zole A, Myxothiazole A.; O3-De-Me, 2,3-dihydro, 3-ketone, Co complex, Micacocidins; Cu complex, Micacocidins; Fe Myxothiazole A: 17, 18-Epoxide, Myxothiazole A; 17Z-Iso complex, Micacocidins; Nicomplex, Micacocidins; Zn com mer, Myxothiazole A; Parent acid, Meester, Myxovalargin, plex, Michiganin A, Microbisporicin, Microcin B17, Micro Myxovirescin A1, Myxovirescin A1; 9-Alcohol, Myxovires cin C, Microcin D93, Microcin E492, Microcin H47, Micro cin A1: 13-Deethyl, 13-methyl, Myxovirescin A1; 13-De cin J25, Microcin L, Microcin N, Microcin V. Micrococcal ethyl, 13-methyl, 4-epimer, Myxovirescin A1: 13-Deethyl, nuclease, Micrococcin GO5, Micrococcin M, Micrococcin 13-methyl, 4-epimer, 9-deoxo, Myxovirescin A1: 33-O-De P1, Micrococcin P1: 17-Ketone, Micromonomycin, Me, Myxovirescin A1: 33-Demethoxy, Myxovirescin A1; Micromonospolide A, Micromonospolide A: 21-O-Deacyl, 33-Demethoxy, 2,3-didehydro, Myxovirescin A1: 17-De Micromonospolide C. Micromonosporin A, Mildiomycin, (methoxymethyl), 17-carboxy, Myxovirescin A1; Mildiomycin; 8-Deoxy, Millericin B. Millipede protein, 33-Demethoxy, 5-oxo, Myxovirescin A1; 9-Deoxo, Myx Mitomycin C; N1-(3-Oxobutyl), Mitomycin C; Stereoiso ovirescin A1; 9-Deoxo, 2,3-didehydro, Myxovirescin A1; mer, Miuraenamide A, Miuraenamide A: 3"-Chloro ana 13-Dethyl, 13-methyl, 9-deoxo, Myxovirescin A1: 2,3-Dide logue, Miuraenamide A: O-De-Me, Miuraenamide A: hydro, Myxovirescin A1; Epimer, Myxovirescn A1; 3R-Hydroxy, Miuraenamide A: 3"-Iodo analogue, Miuraena 4-Epimer, 9-alcohol, Myxovirescin A1: 4-Epimer, 33-O-de mide A; 13Z-Isomer, Mixirin A, Mixirin B, Mixirin C, MLI, Me, Myxovirescin A1: 4-Epimer, 33-demethoxy, Myxovires Mocimycin, Moiramide A, Moiramide B, Monastatin, Mona cin A1: 4-Epimer, 9-deoxo, Myxovirescin A1: 5-Oxo, Myx Zomycin, Monazomycin, N-(Aminoiminomethyl), Mon ovirescin G1, Myxovirescin G1: 4-Demethyl, 7-oxo, ensin; Monensin B, 26-Deoxy, 3-O-de-Me, 3-propanoyl, Myxovirescin G1: 4-Epimer, Myxovirescin K1, Myxovires Monensin; Monensin B, 3-O-De-Me, 3-propanoyl, Monica cin K1: 4-Epimer, Myxovirescin N1, Myxovirescin N1; mycin, Monomethyl-Sulfatase, Morganocin, Morphine 6-de 4-Epimer, Myxovirescin P1, Myxovirescin P1: 4-Epimer, hydrogenase, Morricin 269, MSA 13, Mundticin, Mundticin NAD(+): dinitrogen reductase (ADP-D-ribosyl)transferase, L. Mupirocin F2, Mupirocin H. Mupirocin W. Muramic acid; NADH peroxidase, NAD(+) kinase, NAD(+) nucleosidase, D-form, 1'-Epimer, N. Ac, Muraminomicins, Muramoyl NADPH-cytochrome-c2 reductase, NADPH peroxidase, pentapeptide carboxypeptidase, Muramoyltetrapeptide car Nannochelin C, Nannochelin C; 1,1-Di-Meester, Nannoch boxypeptidase, Musettamycin, Musettamycin; N-De-Me, elin C: 1-Me ester, Naphthalene 1,2-dioxygenase, Naphthos Musettamycin; 10-Epimer, Mutacins; Mutacin B-Ny 266, pironone A, Napyradiomycin A1, Napyradiomycin B1, US 2016/01 86168 A1 Jun. 30, 2016 40

Napyradiomycin B1; 3'-Dechloro. 3'-bromo, Napyradiomy ranosyl-(1->2)-B-D-glucopyranosyl ester, Octahydro-2-hy cin B1; 4a-Dechloro, 4.4a-didehydro, Napyradiomycin B4. droxy-5H,10H-dipyrrolo 1,2-a: 1,2'-dpyrazine-5,10-dione: Napyradiomycin C1, Napyradiomycin C1, A17(19)-Isomer, (2R,5aS,10aS)-form, 1,2,7,7,8,8,11,12-Octahydrolyco 16-chloro, Narine F, Nebularine, Neelaredoxin, Negamycin; pene, Octahydro-7a-methyl-1-(1-methyl-2-oxopropyl)-5- (3R,5S)-form, 5-Deoxy, Neginamycin, C-Neoagaro-oli OXO-1H-indene-4-propanoic acid, Octamycin, Octanethioic gosaccharide hydrolase, Neoantimycin, Neobacillamide A: acid; SH-form, S-Me ester, 5-Octanoylamino-2,3,6(1H)-py (R)-form, Neoberninamycin, Neocidin, Neoenactin; Neoen ridinetrione, Octapeptin A, Octapeptin B, Octapeptin B; actin A, 10'-Alcohol, Neomycin A, Neomycin A; 3'-Deoxy, Octapeptin B5, Octapeptin C, Octapeptin D, trans-Octapre Neomycin A: 3,4'-Dideoxy, Neomycin A; 6'-N-Me. 1-N-(4- nyl-trans-transferase, Octicidin, Octopinic acid, D-glycero amino-2S-hydroxybutanoyl), Neomycin G: 6-Epimer, D-talo-2-Octulosonic acid, Okadaxanthin, Okenone, Oligo 6'-deamino, 6'-hydroxy, Neopullulanase, Neorustmicin B, 1,6-glucosidase, Oligomycin A; 10-Demethyl, 7-alcohol, Neorustmicin C, Neorustmicin D. Neosidomycin; 4-Meth Oligomycin A; 10-Demethyl, 28-oxo, 7-alcohol, Oligonucle oxy, Neosidomycin; 4-Methoxy, 6'-parent acid, 6'-amide, otidase, Oligopeptidase B. Oligosaccharide reducing-end Neosurugatoxin, 5,18-Neoverrucosanediol; (5B, 13C)-form, Xylanase, Olivoretin C, Olivoretin C; O-De-Me, Olivoretin E, 5.9-Neoverrucosanediol; (5.3.9B, 13C.)-form, 5.9, 18-Neover Oncotoxin, Oomycin A, Opine dehydrogenase, Opines; rucosanetriol; (53.93.13.C.)-form, 5.9, 18-Neoverrucosan Epileucinopine, 2-Epimer, Orcinol 2-monooxygenase, Orfa etriol; (5 B.93.13.C.)-form, 18-Aldehyde, Neplanocin A, Nepl mide A, Orfamide A: 10-N-Deacyl, 10-N-(3-hydroxydode anocin B, Neplanocin C, Neplanocin D, Neplanocin F, canoyl), Orfamide A: 7-Valine analogue, Ornibactin C4. Ngercheumicin A, Ngercheumicin A; 4".5"-Dihydro, Ornibactin C6, Ornibactin F. Ornithine aminotransferase, Ngercheumicin C, Ngercheumicin C: 3-Methionine ana Ornithine carbamoyltransferase, Orotate phosphoribosyl logue, Ngercheumicin C: 3-Phenylalanine analogue, Nicoti transferase, Orthosomycin J. Oscillol; 2,2'-Diketone, 1,1'-di namide nucleotide adenylyltransferase, Nicotinate dehydro Me ether, Oxalate CoA-transferase, Oxamate carbamoyl genase, Nicotinate nucleotide adenylyltransferase, transferase, Oxamicetin, Oxaunomycin; 10.11-Dideoxy, Nicotinate-nucleotide:dimethylbenzimidazole phospho-D- 4-Meether, Oxazinomycin, Oxetanocin, Oximidine II, Oxi ribosyltransferase, Nicotinate-nucleotide diphosphorylase midine II; 12C., 13C-Epoxide, Oximidine II; 17E-Isomer, (carboxylating), Nicotinate phosphoribosyltransferase, 14-deoxy, 12C, 13C-epoxide, 3-Oxoacyl-acyl-carrier-pro Nicotine dehydrogenase, Nigrescin, Nisin A, Nisin A; 27-L- tein synthase, 3-Oxoadipate CoA-transferase, 3-Oxoadipate Asparagine analogue, Nisin F. Nisin Q. Nisin U, Nisin U; enol-lactonase, 3-Oxoadipyl-CoA thiolase, 7-Oxo-1-azabi Variant, Nitric oxide dioxygenase, Nitric oxide reductase, cyclo[3.2.0 heptane-2-carboxylic acid; (2R,5R)-form, 5-Nitro-1,3-benzenediol, Nitrogenases, 2-Nitroimidazole, 7-Oxo-1-azabicyclo[3.2.0]heptane-2-carboxylic acid; (2S, 3-Nitroindazole, 2-Nitro-4-(2-nitroethenyl)phenol, 2-Nitro 5R)-form, 7-Oxo-1-azabicyclo[3.2.0]hept-2-ene-2-carboxy 4-(2-nitroethenyl)phenol; 6-Nitro, 4-Nitrophenol, 2-Nitro lic acid; (R)-form, C.-Oxo-1-azetidineacetic acid, 4-Oxobu phenol 2-monooxygenase, Nitrosofungin, NMN nucleosi tanoic acid, 6-OXocineole dehydrogenase, 2-(5-OXo-1- dase, Nocamycin I, Nocamycin I; 8-Alcohol, Nocamycin I; cyclopenten-1-yl)methylbutanoic acid, (2-Oxoethyl) N-Me, Nocapyrone A, Nocapyrone A; 5'-Deoxy, Nocapyrone phosphonic acid, 2-OXo-3-guaien-12,6-olide; (13.5C.6C. C. Nocapyrone C; 6'-Deoxy, Nocapyrone F. Nocapyrone G. 10B,11C)-form, 27-Oxooctacosanoic acid, 2-Oxo-3- Nocapyrone G; 3'-Deoxy, Nocardamine, Nocardicin A; phenylpropanoic acid, 5-Oxoprolinase (ATP-hydrolysing), E-Isomer, Nocardicin E, Nocardicin E; E-Isomer, Nocardicin 2-Oxopropanal, 2-Oxopropyl-CoM reductase (carboxylat G. Nocardioazine A, Nocardioazine B, Nocardiopsin B, ing), 2-Oxo-2H-pyran-4,6-dicarboxylic acid, 3-Oxosteroid Nocardiopsin B; 28-Ketone, Nocardorubin, NodRf III, Nod 1-dehydrogenase, 4,4'-Oxybisbenzenepropanoic acid, 1,1'- Rm 1, 1.2-Nonadecanediol: (S)-form, 2-Tetradecanoyl, 1-O- Oxybis3-4-(methylamino)phenoxy-2-propanol, Paeniba B-D-glucopyranoside, 1.2-Nonadecanedol; (S)-form, cillin, Paenibacillin N, Paenibacillin P. Paenibactin, Paeni 2-Hexadecanoyl, 1-O-B-D-glucopyranoside, 2-(3,7,11,15, macrolidin, Pantetheline; (R)-form, Pantetheine kinase, 19.23.27.31,35-Nonamethyl-2,6,10,14, 18.22.26.30,34 Pantetheline phosphate adenylyltransferase, Pantethine; hexatriacontanonenyl)-1,4-benzoquinone, Nonaprenoxan (R,R)-form, Pantoate 4-dehydrogenase, Pantocin A, Pantocin thin, Nonaprenoxanthin; 11", 12'-Didehydro, A2, Pantocin B, Pantocin B: De?methylsulfonyl), Pantothen 2-Nonaprenylphenol, Nopaline; (R.S)-form, Norchainin, ate kinase, Papulinone, Paracaseicin A, Paromamine, Paro Norcoronatine, Noricumazole A, Noricumazole A, 18-O-O- mamine; 3'-Deoxy, Paromamine; 5-O-B-D-Xylofuranosyl, D-Arabinofuranoside, Noricumazole A, 11-O-B-D-Glucopy Paromomycin; 3-N-Me, Pauciflorol F: 2,3-Didehydro, penta ranoside, Nosiheptide, Nostoxanthin, Nostoxanthin; Meether, PAX Antibiotics; PAX 1, PAX Antibiotics; PAX 10, 2'-Deoxy, 3'-sulfate, Nostoxanthin: 3-O-Sulfate, Nucleoside PAX Antibiotics; PAX 11, PAX Antibiotics; PAX 12, PAX deoxyribosyltransferase, Nucleoside phosphotransferase, Antibiotics; PAX 13, PAX Antibiotics; PAX 2, PAX Antibi Nucleoside ribosyltransferase, Nucleoticidin, Nukacin ISK otics; PAX 3, PAX Antibiotics; PAX 3", PAX Antibiotics; 1, Nukacin KQU-131, Nystatin: Nystatin A1, 28.29-Didehy PAX 4, PAX Antibiotics; PAX 5, PAX Antibiotics; PAX 6, dro, 5-ketone, Oasomycin A, Oasomycin A; 465-Alcohol PAX Antibiotics; PAX 7, PAX Antibiotics; PAX 8, PAXAnti (lactol), 22-O-O-D-mannopyranoside, Oasomycin A; 22-O- biotics; PAX9, PCW, Pedein A, Pedein A; Dechloro, Pedio C-D-Mannopyranoside, Oasomycin A; Parent hydroxyacid, cins, Pediocins; Pediocin 05-10, Pediocins; Pediocin 5, Oasomycin A; Parent hydroxyacid, 22-O-O-D-mannopyra Pediocins; Pediocin A, Pediocins; Pediocin ACCEL, Pedio noside, Oasomycin D, Oasomycin D; 22-O-O-D-Mannopy cins; Pediocin ACM, Pediocins; Pediocin F. Pediocins; ranoside, Obafluorin, Obutin, Occidiofungin A, Occidiofun Pediocin ISK1, Pediocins; Pediocin JD, Pediocins; Pediocin gin A; 3"S-Hydroxy, Ochramycin, Ochrobactin C, L50, Pediocins; Pediocin LB-B1, Pediocins; Pediocin N5p, Ochrobactin C; N-Deacyl, N-octanoyl, Ochrobactin C: Pediocins; Pediocin PA1, Pediocins; Pediocin PD1, Pedio N-Deacyl, N-(2E-octenoyl), 6,11-Octadecadienoic acid; (6E, cins; Pediocin PO2, Pediocins; Pediocin SA131, Pediocins: 11Z)-form, 11-Octadecenoic acid; (Z)-form, B-D-Glucopy Pediocin SJ-1, Pendolmycin, Penocin A, 1,11,19,27,35-Pen US 2016/01 86168 A1 Jun. 30, 2016

taamino-3-tetracontanol, 4.8.12.16.20-PentaaZatricosane-1, acid; 2-Phenylethylamide, Phenylacetohydroxamic acid; 23-diamine, Pentachlorophenol monooxygenase, 5-Pentaco N-Me, Phenylacetyl-CoA dehydrogenase, Phenylacetyl syl-1,3-benzenediol. 2,5,8,11,14-Pentadecanepentone, 1.2.3, CoA hydrolase, Phenylalanine N-acetyltransferase, Phenyla 5,7-Pentahydroxy-6-methylanthraquinone; 1,3-Di-Meether, lanine dehydrogenase, Phenylalanine monooxygenases; Phe 29-(1,2,3,4,5-Pentahydroxypentyl)-29-hopanol; (22S,29R, nylalanine 2-monooxygenase, Phenylalaninylarginal; 31R.32R,33S.34S)-form, 35-O-(2-Deoxy-2-(9-cyclohexyl N2-Ac, Phenylalaninylarginal; N2-(3-Methylbutanoyl), Phe nonanoyl)amino-B-D-mannopyranoside, 29-(1,2,3,4,5- nylalaninylarginal; N2-(2-Methylpropanoyl), Phenylalani Pentahydroxypentyl)-29-hopanol; (22S.29R,31R,32R,33S, nylarginal; N2-Propanoyl, 4-Phenyl-3-buten-2-one; (E)- 34S)-form, 35-O-(2-Deoxy-2-(11-cyclohexylundecanoyl) form, 10-Phenyldecanoic acid, 1-Phenyl-1-decanone, amino-B-D-mannopyranoside. 29-(1,2,3,4,5- 12-Phenyldodecanoic acid, 2-Phenylethylamine; N Ac, Pentahydroxypentyl)-29-hopanol; (22S.29R,31R,32R,33S, 2-Phenylethylamine; N-Butanoyl, 2-Phenylethylamine: 34S)-form, 35-O-(2-Deoxy-2-(13-cyclohexylnonanoyl) N-Hexanoyl, 2-Phenylethylamine; N-(3-Methylbutanoyl), amino)-B-D-mannopyranoside. 29-(1,2,3,4,5- 2-Phenylethylamine; N-(13-Methyltetradecanoyl), 2-Phe Pentahydroxypentyl)-29-hopanol; (22S.29R,31R,32R,33S, nylethylamine; N-Pentadecanoyl, 2-Phenylethylamine; 34S)-form, 35-O-(2-Deoxy-2-(15 N-Tetradecanoyl, N-(2-Phenylethyl)carbamic acid; Et ester, cyclohexylpentadecanoyl)amino-B-D-mannopyranoside. 4-Phenyl-2(5H)-furanone, 16-Phenylhexadecanoic acid, 29-(1,2,3,4,5-Pentahydroxypentyl)-29-hopanol; (22S,29R, 3,3'-(Phenylmethylene)bis-1H-indole, Phenylnannolone A, 31R.32R,33S.34S)-form,35-O-(2-Deoxy-2-(17-cyclohexy Phenylnannolone A, 4-Hydroxy, Phenylmannolone B, 1-Phe lheptadecanoyl)amino-B-D-mannopyranoside, 29-(1.2.3.4. nyl-1,2-propanedione, 3-Phenylpropanoic acid, 1-Phenyl-2- 5-Pentahydroxypentyl)-29-hopanol: (22S,29R,31R,32R, propanone, 14-Phenyltetradecanoic acid, 13-Phenyltride 33S.34S)-form, 35-O-(2-Deoxy-2-(19 canoic acid, Philipimycin, Pholipeptin, Pholipeptin: cyclohexylnonadecanoyl)amino-B-D-mannopyranoside. Stereoisomer, Phosphate acetyltransferase, Phosphate 29-(1,2,3,4,5-Pentahydroxypentyl)-29-hopanol; (22S,29R, butyryltransferase, Phosphatidate cytidylyltransferase, Phos 31R.32R,33S.34S)-form,35-O-(2-Deoxy-2-(21-cyclohexy phatidylcholine synthase, Phosphatidylglycerol membrane lheneicosanoyl)amino-B-D-mannopyranoside, 29-(1.2.3.4. oligosaccharide glycerophosphotransferase, Phosphatidylg 5-Pentahydroxypentyl)-29-hopanol: (22S,29R,31R,32R, lycerophosphatase, Phosphatidylinositol 33S.34S)-form, 35-O-(2-Deoxy-2-(23 C-mannosyltransferase, Phospho-N-acetylmuramoyl-pen cyclohexyltricosanoyl)amino-B-D-mannopyranoside, 2-O- tapeptide-transferase Phosphoenolpyruvate glycerone phos (3,7,11,15,19-Pentamethyleicosyl)-1-O-(3,7,11,15 photransferase, Phosphoenolpyruvate protein phosphotrans tetramethylhexadecyl)glycerol, Pentaneicin, trans ferase, 1-Phosphofructokinase, 6-Phosphofructokinase, Pentaprenyl-trans-transferase, Pentocin TV35b, threo-2- 6-Phosphofructo-2-kinase, 6-Phospho-B-galactosidase, Pentulose: D-form, PepB aminopeptidase, Peptidase Do, 6-Phospho-B-glucosidase, Phosphoglycerate kinase, Phos Peptidoglycan, Peptidoglycan B-N-acetylmuramidase, Pep phoglycerate phosphatase, 3-Phosphoglyceroyl phosphate tidoglycan glycosyltransferase, Peptidyl dipeptidase A, Pep polyphosphate phosphotransferase, Phospholipase C, Phos tidyl dipeptidase Dcp, Peptin31, Perfringocin 11105, Perillyl phomethylpyrimidine kinase, Phosphomevalonate kinase, alcohol dehydrogenase, Permetin A. Permetin A; Analogue Phosphonate dehydrogenase, Phosphopolyprenol glucosyl (1), Permetin A; Analogue (2), Permetin A; 2-L-Valine ana transferase. Phosphoramidate hexose phosphotransferase, logue, Persicomycin, Pertucin, Pesticin, Petrobactin, Petro Phosphoribokinase, Phosphoribosylglycinamide formyl bactin; 2.2"-Disulfo, Petrobactin; 2'-Sulfo, PGL Aglycone; transferase, Phosphoribulokinase, 3-Phosphoshikimate 31-O-B-D-Galactofuranosyl-(1->6)--D-galactofurano 1-carboxyvinyltransferase, Nö-Phosphosulfamylornithine, side, PGLAglycone; 31-O-C-D-Glucopyranosyl-(1->2)-B- O.C.-Phosphotrehalase, Photobactin, Photolumazine B. Pho D-galactofuranoside, PGLAglycone; N-Me, 31-O-B-D-ga tolumazine B: 1'-Deoxy, Photopterin A, Phoxalone, Phthalate lactofuranosyl-(1->6)-B-D-galactofuranoside. PGL 4,5-dioxygenase, 3-Phytase, Phytoene synthase, Phytuberol: Aglycone; N-Me, 31-O-O-D-glucopyranosyl-(1->2)--D- Ac, Piericidin; Piericidin A6, 11'R*,12"R*-Epoxide, Pipeco galactofuranoside. Phagicin, Pharacin, Phaseolotoxin, late dehydrogenases; L-Pipecolate dehydrogenase, Pipeco Phaseolotoxin; 3'-Hydroxy, Phenalamide A1, Phenalamide late dehydrogenases; L-Pipecolate oxidase, Piperazinomy A1: 4Z,6E-Isomer, Phenalamide A1; 6E-Isomer, Phenala cin, Al-Piperideine-2-carboxylate reductase, Piscicocin mide A1; 6E-Isomer, 105,115-epoxide, Phenalamide B, 2.3, CS526, Piscicolin 126, Planothiocin, Plantacin B, Plantar 5,7-Phenanthrenetetrol: 3,5-Di-Me ether, 2,3,5,7-Phenan icins, Plantaricins; Plantaricin 1.25, Plantaricins; Plantaricin threnetetrol; 5,7-Di-Me ether, 1-Phenazinecarboxylic acid, 149, Plantaricins; Plantaricin 423, Plantaricins; PlantaricinA, 1-Phenazinecarboxylic acid; Amide, 1-Phenazinecarboxylic Plantaricins; Plantaricin AMA-K, Plantaricins; Plantaricin acid; 5,10-Dihydro, amide; amide (1:3 complex), 1.6-Phena ASM1, Plantaricins; Plantaricin BN, Plantaricins; Plantaricin Zinedicarboxyhc acid, 1.6-Phenazinedmethanol, 1.6-Phena C, Plantaricins; Plantaricin C19, Plantaricins; Plantaricin D, Zinedimethanol. 1-Carboxylic acid, amide, 1.6-Phena Plantaricins; Plantaricin 35d, Plantaricins; Plantaricin EF, Zinediol. 1,6-Phenazinediol; 5,10-Dioxide, 1,6- Plantaricins; Plantaricin F. Plantaricins; Plantaricin.JK, Plan Phenazinediol; Mono-Me ether, 5,10-dioxide, 1,6- taricins; Plantaricin KW30, Plantaricins; Plantaricin LC74, Phenazinediol; 5-Oxide, 1,8-Phenazinediol, 1.8- Plantaricins; Plantaricin LP84, Plantaricins; Plantaricin MG, Phenazinediol; 10-Oxide, 2,3-Phenazinediol, 2,3,7- Plantaricins; Plantaricin NA, Plantaricins; Plantaricin NC8, Phenazinetriol, 1-Phenazinol, 1-Phenazinol; 10-Oxide, Plantaricins; Plantaricin S, Plantaricins; Plantaricin SA6, 2-Phenazinol, 2-Phenazinol; OH-form, O-(35,7,11,15,19 Plantaricins; Plantaricin SIK83, Plantaricins; Plantaricin T. Pentamethyl-6E, 10E, 14E, 18-eicosatetraenyl), Phenazosta Plantaricins; Plantaricin UG1, Plantaricins; Plantaricin W. tin B: Epimer, Phenol 2-monooxygenase, Phenomycin, Phe PlantazolicinA, Plantazolicin A; N,N-Di-de-Me, Platomycin noXan, Phenylacetaldehyde, Phenylacetaldehyde; A. Platomycin B. Pleuracin ML, Plusbacin A: Plusbacin A1, O-Methyloxime, Phenylacetic acid Amide, Phenylacetic Plusbacin A; Plusbacin A1, 10-Deoxy, Plusbacin A; Plusba US 2016/01 86168 A1 Jun. 30, 2016 42 cin A2, Plusbacin A; Plusbacin A2, 10-Deoxy, Plusbacin A, Proviolacein, Proviolacein; 5-Deoxy, Proximicin A, Proximi Plusbacin A3, Plusbacin A; Plusbacin A3, 10-Deoxy, Plusba cin A; N1-2-(4-Hydroxyphenyl)ethyl, Proximicin A; N1 cin A; Plusbacin A4, Plusbacin A; Plusbacin A4, 10-Deoxy, 2-1H-Indol-3-yl)ethyl, Prumycin, PSC A, Pseudoaltero Pneumocins, Polcillin, Polybromohydroxydiphenyl ethers: bactin A, Pseudoalterobactin B, Pseudobactin 589A, 2.3'4.5'-Tetrabromo-2,6-dihydroxydiphenyl ether, 2-Me Pseudobactin B, Pseudobactin B; 5'-Amide, Pseudobactin B; ether, Polyfermenticin SCD, Poly(glycerol-phosphate) Analogue (R-COCH2CH2CH2NHCOOH), 5,6-dihydro, C-glucosyltransferase, Poly(3-hydroxybutyrate) depoly Pseudobactin B; Analogue merase, Poly(3-hydroxyoctanoate) depolymerase, Polyman (R=COCH2CH2CH2NHCOOH), 7-sulfo, 5,6-dihydro, nuronate hydrolase, Polymyxin B1, Polymyxin B1; Pseudobactin B; 5,6-Dihydro, 5'-amide, Pseudobactin B; N-Deacyl, N-(6-methylheptanoyl), Polymyxin D1, Poly 7-Sulfo, 5,6-dihydro, 5'-amide, Pseudobactin 7SR1, Pseudo myxin D1, N-Deacyl, N-(6-methylheptanoyl), Polymyxin E, bactin 7SR1; 3'-Deoxy, Pseudodeoxyviolacein, Pseudode Polymyxin E: Ile-Polymyxin E1, Polymyxin E: Ile-Poly oxyviolacein; 5-Hydroxy, Pseudodesmin A, Pseudodesmin myxin E2. Polymyxin F. Polymyxin K. Polymyxin M, Poly B, Pseudofactin I, Pseudofactin II, Pseudomonic acid A, myxin P: Polymyxin P1, Polymyxin P: Polymyxin P2, Poly Pseudomonic acid A, 4',5'-Didehydro, Pseudomonic acid A. myxin S1, Polymyxin T1, Polynitroxin, Polynucleotide 5-Hydroxy, Pseudomonic acid A, 4-Ketone, Pseudomonic 5'-phosphatase, Polypeptin A, Polypeptin B, Polyphosphate acid C. Pseudomonine, Pseudomonine; 3'-Hydroxy, Pseudo glucose phosphotransferase, Polyphosphate kinase, Polypre mycin A, Pseudomycin A; 4'-Deoxy, Pseudomycin C, nol; Undecaprenol, Polyprenol; Undecaprenol, O-(2-Amino Pseudomycin C; 4'-Deoxy, Pseudotrienoic acid A. Pseudot 2-deoxy-3-D-galactopyranosyl) phosphate, Poly(ribitol rienoic acid B, Pseudouridine kinase, Psicofuranine, Pterin phosphate) N-acetylglucosaminyltransferase, Poly(ribitol deaminase, Pteroylglutamic acid; Homologue (n=3), Pul phosphate) B-glucosyltransferase, Polyribonucleotide cherriminic acid, Pulcherriminic acid; Fe complex, Pullula nucleotidyltransferase, Achronobacter lyticus Polysaccha nase, Pulvomycin, Pumacin, Pumilicin 4, 2.6-Purinediamine, ride, Bacillus laevolacticus Polysaccharide, Polysaccharide Purine nucleosidase, Purine-nucleoside phosphorylase, Pus RON F. Polysialic acid O-acetyltransferase, Portmicin, Port tulan, Putidolumazine, Putisolvin I, Putisolvin I; 2-Isoleucine micin; 21.25-Dideoxy, 21.25-epoxy, Pradimicin A, N-De or Leucine analogue, Putrescine carbamoyltransferase, Me, Preacinetobactin, Preacinetobactin; 3'-Deoxy, Precorrin Putrescine oxidase, Pyloricidin D. Pyloricidin D; N5-Li 2, Precorrin 4, Precorrin 5, Precorrin 3A, Precorrin 3B, Pre Leucyl, Pyloricidin D; N5-L-Valyl-L-isoleucyl-L-leucyl, corrin 6B, Precorrin-3B synthase, Precorrin methyltrans Pyloricidin D; N5-L-Valyl-L-leucyl, Pyloricidin D; N5-L- ferases: Precorrin-6A synthase (deacetylating), Precorrin Valyl-L-leucyl-L-leucyl, Pyloricidin D; N5-L-Valyl-L-valyl methyltransferases; Precorrin-3B C17-methyltransferase, L-leucyl, Pyochelin I, Pyochelin I; 2-Epimer, Pyocins, Pyo Precorrin methyltransferases; Precorrin-2 C20-methyltrans cyanine, Pyo IV, Pyoluteorin, Pyoluteorin; 3'-Nitro, ferase, Precorrin methyltransferases; Precorrin-4C11-meth Pyoverdin 11370, Pyoverdin 18.1, Pyoverdin 18.1; Homo yltransferase, Precorrin methyltransferases; Precorrin-6Y logue (R= COCH2CH2COCOOH), Pyoverdin 18.1; C5, 15-methyltransferase (decarboxylating), Precorrin 8x. Homologue (R= COCH2CH2COCOOH), 5,6-dihydro, Precorrin 6y, Precorrin 6y: 1,2-Didehydro, Pretaric acid, Pre Pyoverdin 2112, Pyoverdin 2908, Pyoverdin 90-51, Pyover tubulysin D. Pretubulysin D; 4"-Hydroxy, Primycin, Proacti din 90-51: 3'-Hydroxy, 4-amide, Pyoverdin 95-275, Pyover nomycin; Proactinomycin A, Proactinomycin; Proactinomy din 96-312, Pyoverdin 96-312: Amide, Pyoverdin 96-312: cin B. Proactinomycin; Proactinomycin C. Prochlorosins, Homologue (R-COOH), Pyoverdin 96-318, Pyoverdin Prodigiosan, Prodigiosene, Prodigiosin, Prodigiosin; O-De 96-318; Homologue (R-COOH), Pyoverdin 96-318; 3'-Hy Me, Prodigiosin: Demethoxy, Prodigiosin: Homologue droxy, amide (R-NH2), Pyoverdin A1, Pyoverdin BTP 2, (n=5), Prodigiosin; Homologue (n=6), Prodigiosin; Lower Pyoverdin BTP16G, Pyoverdin BTP7G, Pyoverdin C, homologue (n=2), Prodigiosin; Lower homologue (n-3), Pyoverdin CFBP 2392, Pyoverdin CFBP 2461, Pyoverdin Proferrorosamine B. Proferrorosamine B: Fe complex (2:1). CFBP 2461; 3-Hydroxy, Pyoverdin CFML 96.188, Pyover Prohibicin, D-Proline reductase (dithiol), Prolyl oligopepti din CFML 96.188: Homologue, amide, Pyoverdin CFML dase, Promysalin, Promysalin; 2-Deoxy, Promysalin; 96.188: Homologue (R-COOH), Pyoverdin CFML 96.188: 2-Deoxy, 18,19-dihydro, Promysalin; 18, 19-Dihydro, 1,3- 2-Ornithine homologue, amide, Pyoverdin CHAO, Pyover Propanediamine, 2-Propenal, Propeptin, Propeptin: De(pro din CHAO: 4-Amide, Pyoverdin C44H61N13O17. Pyover lylseryl), Propionate CoA-transferase, Propionate kinase, din C44H61N13O17; 4-Amide, Pyoverdin Propioniclins; Propionicin F. Propioniclins; Propionicin GBZ C45H63N11O24, Pyoverdin C45H63N11O24; 4'-Amide, 1. Propioniclins; Propionicin PLG-1, Propioniclins; Propioni Pyoverdin C45H63N11O24; 5-Gly analogue, (17->34)-lac cin SM1, Propioniclins; Propionicin T1, Propionin A, Propi tone, 4'-amide, Pyoverdin C45H63N11O24; (17->34)-Lac oxatin A, 3-Propylmalate synthase, Protein ADP-ribosy tone, 4-amide, Pyoverdin C52H75N15O23, Pyoverdin larginine hydrolase, Protein arginine deiminase, C52H75N15O23; 4'-Amide, Pyoverdin C55H83N17O21, Staphylococcus aureus Protein A, Protein-glutamate methy Pyoverdin C57H85N17O24, Pyoverdin C57E185N17O24; lesterase, Protein-glutamate O-methyltransferase, Protein-L- (4'->4)-Lactam, Pyoverdin D. Pyoverdin D; Amide, Pyover isoaspartate(D-aspartate) O-methyltransferase, Protein-me din D-TR133A, Pyoverdin D-TR133A; Amide, Pyoverdin thionine-S-oxide reductase, Protein-PII D-TR133A; 36-Nor, Pyoverdin D-TR133A; 36-Nor, amide, uridylyltransferase, Protescin, Proticin, Proticin 3, Protocat Pyoverdin G 173, Pyoverdin G 173; 3"-Hydroxy, Pyoverdin echuate dioxygenases; Protocatechuate 3,4-dioxygenase, GM II, Pyoverdin GM II: 3'-Amide, Pyoverdin G4RA, Protocatechuate dioxygenases; Protocatechuate 4.5-dioxy Pyoverdin G4RA, 4-Amide, Pyoverdin I, Pyoverdin II, genase, Protochelin, Protochlorophyllide, Protoporphyrino Pyoverdin II; Amide, Pyoverdin PaC, Pyoverdin Pa II, gen oxidase, Protylonolide, Protylonolide; 19.23-Dihydroxy, Pyoverdin Pa II: 3'-Amide, Pyoverdin Pa TII, Pyoverdin Pf, Protylonolide; 12,13-Epoxide, Protylonolide; 16-Hydroxy, Pyoverdin Pfl2, Pyoverdin Pf 1.3, Pyoverdin Pf 1547, Protylonolide; 195-Hydroxy, Protylonolide; 23-Hydroxy, Pyoverdin Pf3 17400, Pyoverdin Pf/3/2, Pyoverdin Pf/3/2:

US 2016/01 86168 A1 Jun. 30, 2016 44 amino-2S-hydroxybutanoyl), Ribostamycin; 3"-Epimer, N-(6-Methyloctanoyl), N-Seryltyrosine; D-D-form, N-(7- 3',4'-dideoxy, 6'-N-Me, 1-N-(4-amino-2S-hydroxybutanoyl), Methyloctanoyl), Sesbanimide A, Sesbanimide C, Entero Ribostamycin; 3"-Epimer, 2S-hydroxy, 1-N-(4-amino-2S coccus faecalis Sex pheromone cAD1, Enterococcus faecalis hydroxybutanoyl), Ribostamycin; 6'-N-Me, 3-N-(4-amino Sex pheromone cAM373, Enterococcus faecalis Sex phero 2S-hydroxybutanoyl), Ribosylnicotinamide kinase, Ribo mone cocF 10, Enterococcus faecalis Sex pheromone coB1, Sylpyrimidine nucleosidase, Ribulokinase; D-form, Enterococcus faecalis Sex pheromone cD1, Enterococcus Ribulokinase; L-form, Riburonic acid; D-form, Rifamycin, faecalis Sex pheromone inhibitoriaD1, Enterococcus faeca Rifamycin S, Ripostatin A, Ripostatin B. Ripostatin C, Ris lis Sex pheromone inhibitor iAM373, Enterococcus faecalis tomycin A. Ristomycin A; 2C-Deglycosyl, RNA III Activat Sex pheromone inhibitor iCF10, Enterococcus faecalis Sex ing protein, Rodaplutin, Roimatacene, Romidepsin, Rosami pheromone inhibitor iPD1, SF 2809, Sfericase, Shewanel cin, Rosamicin; 20-(AcetylhydraZone), Rosamicin; lose: D-form, Shigellacin 52, Shikimate kinase, Shikome 23-Hydroxy, Rosamicin; 6-Hydroxy(?), Rosecin, Roseobac tabolin A, Shikometabolin B, Shikometabolin C, Shikome ticide A. Roseobacticide A: 4'-Deoxy, Royamicin A. RP tabolin D. Shikometabolin E, Sibiromycin, Sibiromycin; 41200, rRNA N-glycosylase, rRNA methyltransferases: 1,11a-Didehydro, Sibiromycin; 1,11a-Didehydro, 9-O-(4.6- rRNA (adenine-N6)-methyltransferase, rRNA methyltrans dideoxy-3-C-methyl-4-(methylamino)-O-L-mannopyrano ferases; rRNA (guanine-N1)-methyltransferase, rRNA meth side), Sibiromycin; 9-O-(4,6-Dideoxy-3-C-methyl-4-(me yltransferases; rRNA (guanine-N2)-methyltransferase, RU thylamino)-O-L-mannopyranoside), Sibyllimycin, 4.1821, Rubixanthin; (all-E)-form, Rubixanthin; (all-E)- Siderochelin C, Signal peptidase I, Escherichia coli Signal form, 7,8-Dihydro, Rubradirin, Rubredoxin reductases: peptide, Simaomicin B: N-Me, Simplexin, Simusan, Sinefun Rubredoxin-NAD(P)(+) reductase, Rubredoxin reductases: gin VA; 4.5-Didehydro, Siolipin B: Deoxy, Siphonazole A, Rubredoxin-NAD(+) reductase, Rubrifacine, Y-Rubromycin; Siphonazole A: 3'-Me ether, Siroheme, Sirohydrochlorin, 3,3'-Dihydroxy, Y-Rubromycin; 45-Hydroxy, Y-Rubromycin; Sirohydrochlorin; Fe complex, Sirohydrochlorin; Octa-Me 3'-Hydroxy, 3,4-didehydro, 35.45-epoxide, Y-Rubromycin; ester, Sisomicin, Sisomicin; N-De-Me, Sisomicin; 2'-N- 3.3',4-Trihydroxy, Rudolfomycin, Ruminococcin A. Rumi Formyl, Sisomicin; 6'-N-Me, Sisomicin; N-De-Me, 6'-N-Me, nococcin C, S-657, S 365A, S 365A; 2'-Epimer, Safracin A, Sisomicin B, Sisomicin B; 4"-Epimer, SmaPI, SML 91 Lec Safracin A; 7C.-Hydroxy, Saframycin A; 25-Alcohol (1), tin, SNA 60-367, SNA 60-367; SNA 60-367-12, SNA Saframycin A; Decyano. 5C.-methoxy, Saframycin Mx 1. 60-367: SNA 60-367-3, SNA 60-367; SNA 60-367-3, Stere Saframycin Mx 1: 7-Deoxy, Saframycin MX 1; 7-Deoxy, oisomer, SNA 60-367: SNA 60-367-6, SNA 60-367; SNA 1,4-quinone, Saframycin Mx 1: 1,4-Quinone, Sakacins, 60-367-7, Solamacearicin M2. Sorangiadenosine, Sorangi Sakacins; Sakacin 674, Sakacins; SakacinA, Sakacins; Saka cin A, Sorangicin A; 22-Deoxy, Sorangicin A; O21-(6- cin B, Sakacins; Sakacin C2, Sakacins; Sakacin G, Sakacins; Deoxy-B-D-glucopyranoside), Sorangicin A; 22-Deoxy, Sakacin K, Sakacins; Sakacin LSJ618, Sakacins; Sakacin M, O21-?3-D-Glucopyranoside, Sorangicin A; O21-B-D-Glu Sakacins; Sakacin P. Sakacins; Sakacin Q, Sakacins; Sakacin copyranoside, Sorangicin A; 37Z.39E-Isomer, Sorangicin A; T. Sakacins; Sakacin X, Salicylate 1-monooxygenase, Sali 39E-Isomer, Sorangicin A; 41E-Isomer, Sorangicin A; 39E, vacin 140, Salivaricins, Salivaricins; Salivaricin 9, Salivar 41E-Isomer, O21-(6-deoxy-3-D-glucopyranoside), Sorangi icins; Salivaricin A, Salivaricins; Salivarcin A2, Salivaricins; cin C; (37E,39E.41E)-form, Sorangicin C; (37E,39E,417)- Salivaricin B, Salivaricins; Salivaricin CRL1328, Salivar form, Sorangicin C; (37E.39Z.41E)-form, Sorangiolide A, icins; Salivaricin D. Salivaricins; Salivaricin G32, Salivar Sorangiolide A: 6-Hydroxy, Soraphen A, Soraphen A; 10-O- icins; Salivaricin P. Salmochelin 1, Salmochelin 2, Salmoch De-Me, Soraphen A; 11-O-De-Me, Soraphen A; 11-O-De elin 4, Salmochelin X, Saltavalin, Samandaridine, Me, stereoisomer(?), Soraphen A; Derivative, Soraphen A; Sandramycin, Sanguicin, Saproxanthin, Saproxanthin; 1'-O- 10, 11-Di-O-de-Me, Soraphen A; 10, 11-Di-O-de-Me, stere Glucoside, Saproxanthin; 1'-Me ether, Saproxanthin; 1'-O- oisomer(?), Soraphen A; 10.11-Di-O-de-Me, stereoisomer Rhamnoside, Saquayamycin Z. Sarcinapterin, Sarcinaxan (?), Soraphen A; 10.11-Di-O-de-Me, stereoisomer(?), Sor thin, Sarcinaxanthin; Di-O-B-D-Glucopyranoside, aphen A; 12,13-Dihydro, Soraphen A; 12,13-Dihydro, 11-O- Sarcinaxanthin; 7.8-Dihydro, Sarcinaxanthin; Mono-O-B-D- de-Me, Soraphen A; 12,13-Dihydro, 18-O-de-Me, Soraphen Glucopyranoside, Sarcosine dehydrogenases; Sarcosine oxi A: 12,13-Dihydro, 13, 14-didehydro, 125-hydroxy, 10-O-de dase, Sarcosine reductase, SATS 6504, Sattazolin; (+)-form, Me, Soraphen A; 12,13-Dihydro, 7,8-didehydro, 135-hy Sattazolin; (+)-form, Meether, Saxitoxin; N1-Hydroxy, SB droxy, 11-O-de-Me, Soraphen A; 12,13-Dihydro, 10,11-di 29.1071, SB 2.91071; Homologue (R= C11H21), SB O-de-Me, Soraphen A; 12,13-Dihydro, 135-hydroxy, 29.1071; Homologue (R= C13H25), SB 29.1071; Homo Soraphen A; 12,13-Dihydro, 135-hydroxy. 10, 11-bis-O-de logue (R= C15H29), SB 2.91071; Homologue (R= -(CH2) Me, Soraphen A; 12,13-Dihydro, 125-hydroxy, 10-O-de-Me, 10CH3), SB 29.1071; Homologue (R= -(CH2)12CH3), SB Soraphen A; 12,13-Dihydro, 135-hydroxy, 11-O-de-Me, Sor 315021, Sch 351448, Schizokinen, Schizokinen; N-De-Ac, aphen A; 12,13-Dihydro, 135-hydroxy, 10,11-di-O-de-Me, N-(2-decenoyl), Schizokinen; N-Deoxy, Schizokinen A, 3,4, 11-ketone, Soraphen A; 125,135-Epoxide, 11-O-de-Me, Sor 8, 15-Scirpenetetrol; (3C.43,8C)-form, 4.8-Di-Ac, Sedohep aphen A; 85-Hydroxy, Soraphen A; 20-Hydroxy, 11-O-de tulokinase, Sedolisin, Selenate reductase, Selenide, water Me, Soraphen A; 85-Hydroxy, 10-O-de-Me, Soraphen A; dikinase, Selenomethionine: (S)-form, Selenomycin, Serine; 8-Hydroxy, 11-O-de-Me, Soraphen A; 3"-Hydroxy, di-O- (S)-form, N-(3-C-Glucosyl-5,6-dihydroxybenzoyl), Me de-Me, Soraphen A; 85-Hydroxy, stereoisomer(?), Soraphen ester, Serine O-acetyltransferase, Serine-type-D-Ala-D-Ala A: 85-Hydroxy, stereoisomer(?), Soraphen A; 12-Methoxy carboxypeptidase, Serracin P. Serrapeptase, Serratamic acid, (Z-), 11-O-de-Me, Soraphen A; Stereoisomer(?), Soraphen Serratamolide A, Serratamolide B, Serratamolide C, Serrata R, Soraphen R; 10,11-Di-Meether, Soraphen R; 10-Meether, mollide D, Serratamolide E. Serratamolide F, Serratigen, Ser Sorbistin D, Sorbistin D; 4'-N Ac, Sorbistin D; 4'-N-Bu ratiochelin, Serrationycin, Serrawettin W2, L-Seryl-tR tanoyl, Sorbistin D; 4'-Deamino. 4'-hydroxy, Sorbistin D; NASec selenium transferase, N-Seryltyrosine; D-D-form, 4'-N-Propanoyl, Sorbose: L-form, Sorbose dehydrogenases: US 2016/01 86168 A1 Jun. 30, 2016

Sorbose dehydrogenase-form, SP 127, SP 2259, Sperabillin dehydrogenases; Sulfite dehydrogenase, Sulfite reductases; C. Sperabillin C: 4'Z-Isomer, Sperabillin D. Sperabillin D; Sulfite reductase, Sulfite reductases; Sulfite reductase 4Z-Isomer, Spergualin, Spergualin; 15-Deoxy, Spermidine, (NADPH), Sulfoacetaldehyde acetyltransferase, 4-Sulfoben Spermidine; N.N"-Bis(2,3-dihydroxybenzoyl), Spermidine Zoate 3,4-dioxygenase, N-Sulfoglucosamine-3-sulfatase, dehydrogenase, Spermidine synthase, SPF 1010, SPF 140, Sulfolobusquinone, Sulfur dioxygenase, Sulfur reductase, SPF 100 FI, SPF 100 FII, SPF PCO 20, SPF PCO30, Sphe Superoxide reductase, Surfactin, Surfactin; Surfactin B1, roidene, Spheroidene; (15Z,15'Z)-form, Spheroidene: O-De 4-L-Alanine analogue, Surfactin; Surfactin B2, 4-L-Alanine Me, Spheroidene; 11", 12'-Dihydro, Spheroidene; 3.4.11", 12'- analogue, Surfactin; Surfactin B2, 1-Me ester, Surfactin; Sur Tetrahydro, Spheroidenone, Spheroidenone; O-De-Me, factin C1, Surfactin; Surfactin C1, 4-L-Alanine analogue, Spheroidenone; 1,2'-Dihydro, 1'-hydroxy, Sphingomyelin Surfactin; Surfactin C1, 7-L-Isoleucine analogue, Surfactin; phosphodiesterase D, Spirangien A, Spirangien B. Spirillo Surfactin C1, 7-L-Valine analogue, Surfactin; Surfactin C2, mycin; Spirillomycin 1655, Spirillomycin; Spirillomycin 4-L-Alanine analogue, Surfactin; Surfactin C2, 7-L-Valine 1309 b. Spirobrassinol; Meether, N-methoxy, Spirobrassi analogue, 1-Me ester, Surfactin; Surfactin C2, 1-Me ester, nol; N-Methoxy, Spirodienal, Spirodienal: 4E-Isomer, Spiro Sutilains, Synpron, Syringacins, Syringacins; Syringacin 4A, dienal B, Spiruchostatin A, Spiruchostatin B, SpolVB pepti Syringacins; Syringacin W1, Syringafactin A, Syringolide 1. dase, 13, 15-Spongianediol; 13C-form, Sporacuracin A, Syringolide 2, Syringolide 3, Syringolin A, Syringolin A; Sporacuracin B, Sporamycin, Sporangirosomycin, Sporaviri 2,3-Dihydro, Syringolin C, Syringolin D, Syringolin D; 2.3- din; Sporaviridin A1, Sporaviridin; Sporaviridin A1, Dihydro, Syringolin F, Syringomycin, Syringopeptin 22A, 4D-Deoxy, 4D-amino, Sporaviridin; Sporaviridin A1, Syringopeptin 25A, Syringopeptin25A; 25-L-Phenylalanine 6D-Hydroxy, Sporaviridin; Sporaviridin A2, Sporaviridin; analogue, Syringopeptin 22B, Syringopeptin 25B, Syrin Sporaviridin A2, 4D-Deoxy, 4D-amino, Sporaviridin; Spo gopeptin SC 1, Syringopeptin SC 2, Syringostatin, Syrin raviridin A2, 6D-Hydroxy, Sporocuracin A, Sporocuracin B, gostatin: Syringostatin A, 3-Glycine analogue, Syringostatin: Sporulene A, Sporulene A, 16,17-Dihydro, 17O-hydroxy, Syringostatin F, 3-Glycine analogue, Szentiamide, Tabtoxin, Sporulene A: A 15-Isomer, Sporulene A: A 17(35)-Isomer, Tagatose; D-form, Tagatose kinase, Tagatose 6-phosphate Sporulene A. 16, 17.24.27-Tetrahydro, 17C.-hydroxy, Spoxa kinase, Tagetitoxin, Taitomycin, Takanawaenes; Zomicin A, Spoxazomicin A; 2-Epimer, SSL 91 Lectin, Sta Takanawaene C, Tallysomycin; Tallysomycin A, Tallysomy copin P1, Stacopin P1: 4-Hydroxy, Stalobacin, Staphopain, cin; Tallysomycin Sla, Tallysomycin; Tallysomycin Sla, Staphylococcal acid glycoprotein, Staphylococcins, Staphy No-Me, Tallysomycin; Tallysomycin Sla, Nc)-(1-Phenyl lococcins; Staphylococcin 414, Staphylococcins; Staphylo ethyl), Tallysomycin; Tallysomycin Sla, Nc)-(2-Hydroxy coccin 462, Staphylococcins; Staphylococcin A, Staphylo ethyl), Tallysomycin; Tallysomycin S10a, Tallysomycin; Tal coccins; Staphylococcin Au-26, Staphylococcins; lysomycin S2a, Tallysomycin; Tallysomycin S1b, Staphylococcin BacR1, Staphylococcins; Staphylococcin Tallysomycin; Tallysomycin S1b, No.Nc)-Di-Me, Tallyso C55, Staphyloferrin A, Staphyloferrin B, Staphylokinase, mycin; Tallysomycin S1b, No)-(1-Phenylethyl), Tallysomy Starch synthase, Staurosporine; 5'C.-Hydroxy, Staurosporine; cin; Tallysomycin S1b, No-Me, Tallysomycin; Tallysomycin 5'C-Hydroxy, N-Me, Staurosporine; 10-Methoxy, Stauro S1b, No.Nco-Bis(2-hydroxyethyl), Tallysomycin; Tallyso sporinone, Staurosporinone; N13-(C-L-Rhamnopyranosyl), mycin S1b, No)-(2-Hydroxyethyl), Tallysomycin; Tallyso Steffimycin, Steffimycin; (Deglycosyloxy), 2-demethoxy, mycin S10b, Tallysomycin; Tallysomycin S12b, Tallysomy 105-alcohol, Steffimycin; 2-Demethoxy. 105-alcohol, Stella cin; Tallysomycin S13b, Tallysomycin; Tallysomycin S2b, lysin, D-Stereospecific aminopeptidase, Stewartan, Stigma Tallysomycin; Tallysomycin S3b, Tallysomycin; Tallysomy tellin A, Streptimidone, Streptin, Streptindole, Streptindole; cin S3b, No)-(2-Hydroxyethyl), Tallysomycin; Tallysomycin O-De-Ac, O-butanoyl, Streptindole; Deacetoxy, Streptococ S3b, No)-(2-Hydroxypropyl), Tallysomycin; Tallysomycin cin A-M49, Streptococcin A-M57, Streptococcin Sal P. S4b, Tallysomycin K1, Tallysomycin K2, Tallysomycin K3, Streptodornase, Streptokinase, Streptomodulin, Streptomy Tallysomycin K4, Tallysomycin K5, Tambjamine A. 1"-N- cin 3"-adenylyltransferase, Streptonigrin: N7-(1-Methyl-2- (3Z-Dodecenyl), TAN 1057A, TAN 1057A: 5-Epimer, Tar oxopropyl), Streptopain, Streptothricin; Streptothricin F, trolone A1, Tartrolone A1: Stereoisomer (1), Tartrolone A1; N5-Me, Strevertenes; Strevertene A, Strevertenes; Stre Stereoisomer (2), Tartrolone B, Tatiopterin; Tatiopterin 1, vertene B, Strevertenes; Strevertene C, Strevertenes; Stre Tatiopterin; Tatiopterin O, Tatiopterin; Tatiopterin O, 2',5'- vertene D, Strevertenes; Strevertene E. Strevertenes; Stre Dihydroxy, Tatumine, Tauramamide, Taurine dioxygenase, vertene E, 7-Deoxy, 9-hydroxy, Strevertenes; Strevertene F. Taurine transaminases; Taurine 2-oxoglutarate transaminase, Sublancin 168, Subpeptin JM4. Subsporin A. Subsporin B, Taurine transaminases; Taurine pyruvate aminotransferase, Subsporin C. Subtenolin, Subtilin, Subtilin; 6-Valine, 15-va Tecogalan, Teicoplanin, Teicoplanin; Teicoplanin A2-2, line, 24-isoleucine, 29-histidine analogue, Subtilisins; Sub 15-Deamino, 15-oxo, Teicoplanin; Teicoplanin A2-3, tilisin BPN1, Subtilisins; Subtilisin Carlsberg, Subtilisins: 15-Deamino, 15-oxo, Teicoplanin; Teicoplanin A2-3, 4',5'Z- Subtilisin ISP. Subtillosin A. Subtulene A. Succinamopine; Didehydro, 15-deamino, 15-oxo, Teicoplanin; Teicoplanin (2R,2S)-form, Succinamopine; (2S,2S)-form, Succinate A2-4, 15-Deamino, 15-oxo, Teicoplanin; Teicoplanin A2-5, citramalate CoA-transferase, Succinic acid, Succinic acid; 15-Deamino, 15-oxo, Teleocidin B1; 16, 19-Diepimer, Teleo Diamide, Succinoglycan, Succinopyoverdin 18.1. Succino cidin B1; 16-Epimer, Teleocidin B1; 19-Epimer, Teleocidin pyoverdin G173, N-Succinylarginine dihydrolase. Succinyl B1; 16-Epimer, N-de-Me, Teleocidin B1; 16-Epimer, Me CoA:(R)-2-benzylsuccinate CoA-transferase. Succinyl ether, Teleocidin B1; Meether, Tenacibactin B, Tenacibactin diaminopimelate transaminase. Sucrose: 1,6-O-glucan 3(6)- B; Me ester, Tenacibactin C, Tenacibactin D, Terephthalate C-D-glucosyltransferase. Sucrose phosphorylase, Sugar 1,2-dioxygenase, 3.2:2(3'H).3"-Ter-1H-indol-3-one, 3.3': phosphatase, Sugar-terminal-phosphatase, Sulcatone 3'(2H).3"-Ter-1H-indol-2- one, Tetanolysin, 3,3',5,5'-Tet reductase, Sulfate adenylyltransferase, Sulfate adenylyltrans raacetyl-2,2',4,4,6,6'-hexahydroxydiphenylmethane, 4.8.12. ferase (ADP), Sulfazecin, Sulfazecin; 2'-Epimer, Sulfite 16-Tetraazanonadecane-1,19-diamine, 2,3,5,7-Tetrabromo

US 2016/01 86168 A1 Jun. 30, 2016 47 dihydroxy-6-methylbenzoyl), Triacetate-lactonase, 2.4.6- Tryptophan C.f3-oxidase, Tryptophan oxygenases; Tryp Triacetyl-1,3,5-benzenetriol, 4.8, 12-Triazapentadecane-1, tophan 2-dioxygenase, Tryptophan oxygenases; Tryptophan 15-diamine, 1,3,5-Triazine, 2,2,3-Tribromo-4,4'- 2-monooxygenase, Tryptophan transaminases; Tryptophan biphenyldicarboxylic acid, 2,4,4-Trichloro-2'- phenylpyruvate transaminase, Tryptophan transaminases; hydroxydiphenyl ether, Trichrysobactin (cyclic), Tryptophan transaminase, Tubercidin, Tubulysins; Tubulysin Trichrysobactin (linear), 5-Tricosyl-1,3-benzenediol, Tride A, Tubulysins; Tubulysin A, 4'-Deoxy, Tubulysins; Tubulysin captin A, Tridecaptin B, Tridecaptin C, 2.3.6-Trideoxy-3- B, 4'-Deoxy, Tubulysins; Tubulysin C, Tubulysins; Tubulysin dimethylamino-ribo-hexose: L-form, Trifolitoxin, Trihexo C. 4-Deoxy, Tubulysins; Tubulysin G. Tubulysins; Tubulysin cin, 2',4',6'-Trihydroxyacetophenone, 13.8- I, Tubulysins; Tubulysin I, 4'-Deoxy, Turnagainolide A, Tur Trihydroxyanthraquinone, 1.3,8-Trihydroxyanthraquinone; nagainolide A: 15-Epimer, Tuscolide, Tuscorone B, Tus 1,3-Di-Meether, 1.3,8-Trihydroxyanthraquinone; 3.8-Di-Me corone B: 17-Deoxy, 17, 18-didehydro, TV 110, TV 130, ether, 1.3,8-Trihydroxyanthraquinone: 1-Meether, 1,4,5-Tri Tylosin B; 4A-Deoxy, 12C.,13-dihydro, 20-alcohol, Tylosin hydroxyanthraquinone, 1.4.6-Trihydroxyanthraquinone; B; 4A-Deoxy, 12C., 13C-epoxide, 20-alcohol, Tylosin B; 4-Me ether, 3,4,5-Trihydroxybenzoic acid; Dodecyl ester, 20-Deoxo, 4A-deoxy, Type III site-specific deoxyribonu 3,4,5-Trihydroxybenzoic acid; Octyl ester,3,4,5-Trihydroxy clease, Type II site-specific deoxyribonuclease, Type I site benzoic acid; Propyl ester, 3.7.12-Trihydroxycholan-24-oic specific deoxyribonuclease, Typhimuricin, Tyrocidine; 5-Li acid; (3C.5C,7C,12C.)-form, Meester, 2,3,4-Trihydroxy-2,4, Lysinetyrocidine A, Tyrocidine; Tryptocidine A, Tyrocidine: 6-cycloheptatrien-1-one; 3,4-Di-Meether,3,4,6-Trihydroxy Tryptocidine B, Tyrocidine: Tyrocidine A, Tyrocidine: Tyro 1,2-dimethylcarbazole; 3,6-Di-Meether, 3,4,6-Trihydroxy cidine B, Tyrocidine: Tyrocidine B1, Tyrocidine: Tyrocidine 1,2-dimethylcarbazole; Tri-Me ether, 3,4',7- C, Tyrocidine; Tyrocidine C1, Tyrocidine: Tyrocidine D. Trihydroxyisoflavanone; (R)-form, 4',5,7- Tyrocidine: Tyrocidine E. Tyrosylvalylprolyleucine, Tyro Trihydroxyisoflavone, 4.5,7-Trihydroxyisoflavone; 3',5'- thricin, Ubericin A, Uberolysin, UDP-2-acetamido-4-amino Dinitro, 4,5,7-Trihydroxyisoflavone; 3'-Nitro, 4',7,8- 2,4,6-trideoxyglucose transaminase, UDP-N-acetylglu Trihydroxyisoflavone; 7-O-O-D-Arabinofuranoside, 6,7,8- cosamine 1-carboxyvinyltransferase, UDP Trihydroxy-3-methyl-1H-2-benzopyran-1-one: 7-Me ether, N-acetylglucosamine diphosphorylase, UDP-N-acetylmu 1,6,10-Trihydroxy-8-methyl-5,12-naphthacenedione, 2.3.5- ramoylpentapeptide-lysine N6-alanyltransferase, UDPglu Trihydroxy-6-methylpyridine, 2.5,8-Trihydroxy-1,4-naph cose hexose 1-phosphate uridylyltransferase, Ulbactin A, thoduinone, 9,12,13-Trihydroxy-10, 15-octadecadienoic Ulbactin B, Ulbactin C, Ulbactin D, Ulbactin E, Ulceracin acid; (9S.10E, 12R,13S,15Z)-form, 3,4,5-Trihydroxy-2-pen 378, UMP kinase, 1422,26,29,33,4150,58,62,65,69-Un tanone; (3S4R)-form, 2.3.9-Trihydroxy-1-phenazinecar decamethyl-8, 11,44.47-tetraoxahexacyclo68.2.1.12.5.118, boxylic acid, 2,3,7-Trihydroxy-1,6-phenazinedicarboxylic 21.134.37.154.57 heptaheptacontane-10.46-dimethanol, acid, 3.17.21-Trihydroxypregnane-1120-dione; (3C.5 B)- Undecaprenol kinase, Undecaprenyldiphosphomu form, 4-(1,2,3-Trihydroxypropyl)-2(5H)-furanone; 3'-Hex ramoylpentapeptide B-N-acetylglucosaminyltransferase, anoyl, 4-(1,2,3-Trihydroxypropyl)-2(5H)-furanone; 3-Oc Undecaprenyl-phosphate galactose phosphotransferase, tanoyl, 1,1,3-Tri-(1H-indol-3-yl)butane: (S)-form, 1,1,1-Tri Undecaprenyl-phosphate mannosyltransferase, Undecylpro (1H-indol-3-yl)ethane Tri-1H-indol-3-ylmethane, digiosin, Unnarmicin A, Unnarmicin C, Uracil phosphoribo Trimethylamine N-oxide reductases; Trimethylamine-N-ox Syltransferase, Ureidoglycolate dehydrogenase, Ureidogly ide reductase, 2-(3,7,11-Trimethyl-2,6,10-dodecatrienyl)- colate hydrolase, Uridine diphosphate mannose, Uridine 1H-indole; (E.E)-form, Trimethyloxazole, Trimethylpropy kinase, Uridine phosphorylase, Urocanic acid; (E)-form, lpyrazine, Trimethylsulfonium-tetrahydrofolate Uronate dehydrogenase, Uroporphyrin III, Uroporphyrino N-methyltransferase, 3,5,7-Trioxooctacosanoic acid, Tripep gen-Ill C-methyltransferase, Urukthapelstatin A, UTP glu tide aminopeptidase, Triphosphoribosyl-dephospho-CoA cose 1-phosphate uridylyltransferase, UTP hexose 1-phos synthase, Tripropeptin, Tris(3-aminopropyl)amine, Tris(3- phate uridylyltransferase, Valindolmycin, Valine aminopropyl)amine; N-(3-Aminopropyl), 2.3.5-Tris(meth transaminases; Valine pyruvate transaminase, Valylleucyl ylthio)-1,4-benzenediol, 2,3,5-Tris(methylthio)-1,4-ben prolylvalylprolylglutamine, Valylprolylisoleucine; L-L-L- Zenediol; 6-(Methylthio), 2,3,5-Tris(methylthio)-1,4- form, Valylprolyleucine: L-L-L-form, Vanchrobactin, Vanil benzenediol: 1,4-Quinone, 2,3,5-Tris(methylthio)-1,4- late monooxygenase, Variacin, Venturicidin B; 17-Hydroxy, benzenediol: 1,4-Quinone, 6-(methylthio), Trivanchrobactin, 3'-carbamoyl, Verdamicin, Verdamicin; 1-N-Et, Verdamicin; tRNA isopentenyltransferase, tRNA methyltransferases: 6'-N-Me, Vibriobactin, Vibriobactin: 3',3'-Dideoxy, Vibrio tRNA (cytosine-5)-methyltransferase, tRNA methyltrans cins, Vibrioferrin, Vicibactin, Vicibactin: N-De-Ac, Victomy ferases; tRNA (guanine-N1)-methyltransferase, tRNA meth cin, Vilian, 1-Vinyl-f-carboline-3-carboxylic acid, Viola yltransferases; tRNA (guanine-N7)-methyltransferase, cein, Violacein: Deoxy, Violacein: 3,3'-Dihydro, Violacein; tRNA methyltransferases; trNA guanosine-2'-O-methyl 5-Hydroxy, Vioprolide A, Vioprolide B, Vioprolide C. Vio transferase, tRNA methyltransferases; tRNA (5-methylami prolide D. Viridicin, Viridins; Viridin A, Viridins; Viridin B, nomethyl-2-thiouridylate)-methyltransferase, tRNA methyl Viridins; Viridin C, Viriplanin, Viscosin, Viscosin; 5-D- transferases; thNA (uracil-5)-methyltransferase, tRNA Leucyl epimer, Viscosinamide, Vitamin B12, Vitamin B12f; nucleotidyltransferase, tRNA sulfurtransferase, tRNA-uri 176-Demethyl, Vitamin B12 monocarboxylic acid, Vitamin dine aminocarboxypropyltransferase, Tropinesterase, K2: Vitamin K2(40), Vomifoliol 4'-dehydrogenase, Vulnifi Tropodithietic acid, Tropolone, Troposulfenin, Troposulfe cin, Warnericin RB4, Warnericin RK, Warnerin, Warnerin, nin; 8-S-Me, Tryptamine; Nb-Ac, Tryptamine; Nb-Di-Ac, Weissellicins; Weissellicin 110, Weissellicins; Weissellicin Tryptamine; Nb-(2S-Hydroxy-3S-methylpentanoyl), M, Weissellicins; Weissellicin N23, Weissellicins; Weisselli Tryptamine; Nb-(3-Methylbutanoyl), Tryptamine; Nb-(3- cinY. Weissellin A. Welan, Xaa-Pro aminopeptidase, Xaa-Pro Methyl-2-oxopentanoyl), Tryptophan: (S)-form, NC.-(9Z dipeptidase, Xaa-Pro dipeptidyl peptidase, Xaa-Xaa-Pro trip Hexadecenoyl), Tryptophan: (S)-form, NC.-Hexadecanoyl, eptidyl peptidase, Xanthacin, Xanthan, Xanthellin, Xanthine

US 2016/01 86168 A1 Jun. 30, 2016 49

Gentiobiosylglucose: B-D-(2R)-form, Glucolipsins; Mycolactone F: 14-Methyl, Mycolactone F: 14-Methyl, 13'- Glucolipsin B, 3-O-O-D-Glucopyranosyl-L-rhamnose, ketone, Mycolactone F: 17-Oxo, 8.9'-dihydro, Mycosero Glutamate dehydrogenases; Glutamate dehydrogenase sate synthase, Mycothiol, Mycothiol: N-De-Ac, N-(3-car (NADP(+)), Glycerol kinase, Glycerol trihexadecanoate, boxypropanoyl), Mycothiol: N-De-Ac, N-formyl, Mycothiol Glycine dehydrogenases; Glycine dehydrogenase, Glycocin bimane, Mycothione reductase, Myomycin A, Myomycin B, naspermicidin A, Glycocinnaspermicidin A; 4'-O-Deglyco Myomycin B; Homologue (n=3), Myomycin B; Homologue syl, Glycolipid A1, Mycobacterium avium Glycopeptidol (n=4), Myomycin B; Homologue (n=5), Myomycin C, NAD ipid, Glycopeptidolipid X1, Guanosine-3',5'-bis (+) kinase, Nanaomycin A, (-)-form, Nanaomycin A; (+)- (diphosphate) 3-diphosphatase, 5,13-Halimadien-15-ol; form, Nargenicin B1, Nargenicin B2, Nargenicin B3, Neoci (ent-13E)-form, 2.4.6.8,10,12,14-Heptamethyltriacontanoic treamicin I, Neocitreamicin I: 2-O-(4-O-Acetyl-2,6-dideoxy acid; (all-S)-form, Heptaprenylcycline, Heptaprenylcycline; B-D-galactopyranoside), 2-Nitroimidazole, 4-Nitrophenol 18-Oxo, Heterobactin A; N2-Deacyl, N2-(2,3-dihydroxyben 2-monooxygenase, Nocamycin I, Nocamycin I; 8-Alcohol, Zoyl), 2-(3,7,11,15,19,23-Hexamethyl-25-(2,6,6-trimethyl Nocardamine, Nocardenone, Nocardianin, Nocardichelin A, 2-cyclohexenyl)pentacosa-2.14, 18.22-tetraenyl-3-methyl-1, Nocardichelin A; Lower homologue (n=10), Nocardicin A, 4-naphthoduinone. Histidomycin A. N-Hydroxyaspartic Nocardicin A; E-Isomer, Nocardicin C, Nocardicin D, acid: (S)-form, 3-Hydroxyeicosanoic acid; (R)-form, Nocardicin E, Nocardicin E; E-Isomer, Nocardicin G, Hydroxymethylglutaryl-CoA reductases; Hydroxymethyl Nocardicyclin A, Nocardicyclin A; 4'-Ac, Nocardicyclin A; glutaryl-CoA reductase, 6-Hydroxy-1-phenazinecarboxylic Stereoisomer, 10-alcohol, Nocardimicin, Nocardimicin; acid, 4-(2-Hydroxyphenyl)butanoic acid, 5-Hydroxy-2-py Nocardimicin B. Ni-Deoxy, Nocardimicin; Nocardimicin D, ridinecarboxylic acid, 3-Hydroxy-2,4,6-trimethyltetra N1-Deoxy, Nocardimicin; Nocardimicin D. 9", 10'-Dihydro, cosanoic acid; (2S,3R.4S,6S)-form, Indisocin, Indisocin: N-de-Ac, N-formyl, Nocardimicin; Nocardimicin F, 9', 10'- N-Me, Isochelocardin, Isoglutamine; (R)-form, Isonargeni Dihydro, N-de-Ac, N-formyl, Nocardimicin; Nocardimicin cin A1, Isonocardicin synthase, 2-Isopropylmalate synthase, F. N-De-Ac, N-formyl, Nocardimicin; Nocardimicin F, IZupeptin, Kanglemycin A, Kanglemycin C, Kasugamycin, Homologue (R= -(CH2)16CH3), 9,10-dihydro, N-de-Ac, 4-Keto-y-carotene, Lactate 2-monooxygenase, Luridomycin, N-formyl, Nocardione A: (S)-form, Nocardione A: (S)-form, Lysine: (S)-form, 6-N-Hydroxy, Macbecin II, Macbecin II; Me ether, Nocardithiocin, Nocardodienone, Nocardorubin, 18.21-Quinone, Maduramicin, Maduramicin; O5-De-Me, Nocardotrienone, Nocarsine A, Nocobactin NA, Nodusmi Maduramicin; 28-Epimer, Maduramicin; O29-Me, Malate cin, Nodusmicin; 18-Ac, Nodusmicin; 19.20-Dimethoxy, synthase, Mannimositose, 6-O-C-D-Mannopyranosyl-D- 9-O-(1H-pyrrole-2-carboxylate), Nodusmicin; 9-O-(1H mannose, Mannose 1-phosphate guanylyltransferase, B-D- Pyrrole-2-carboxylate), Nodusmicin; 9-O-(1H-Pyrrole-2- Mannosylphosphodecaprenol:(1->6)-C-D-mannosyloli carboxylate), 18-Ac, Noformicin; (+)-form, Nonylprodigi gosaccharide (1->6)-C-D-mannosyltransferase, osin, NS, N T 1, 9-Octacosenoic acid; (Z)-form, Mavioquinone, Maytansinol: 3-Ac, Maytansinol: 3-Bu 2-Octadecanol; (+)-form, 3-Octadecyl-4-tridecyl-2-oxet tanoyl, Maytansinol; Dechloro, 4.5-deepoxy, 4.5-didehydro, anone; (3R,4R)-form, Octahydroheptaprenol. 7,7,8,8,11, Maytansinol; Dechloro, 4.5-deepoxy, 4.5-didehydro, N-de 11,12,12'-Octahydrolycopene, Ornithine carbamoyltrans Me, Maytansinol; 4.5-Deepoxy. 4.5-didehydro, N-de-Me, ferase, 3-OXosteroid 1-dehydrogenase, Pantothenate kinase, Maytansinol; N-De-Me, 3-Ac, Maytansinol; N-De-Me, 3-O- 4,8,12,16.20-Pentamethyl-1-heptacosanol: (all-S)-form, (3-methylbutanoyl), Maytansinol; N-De-Me, 3-O-(2-meth O-(B-D-Mannopyranosylphosphate), 4,8,12,16.20-Pentam ylpropanoyl), Maytansinol; N-De-Me, 3-propanoyl, May ethyl-1-pentacosanol; (all-S)-form, O-(B-D-Mannopyrano tansinol; 15R-Hydroxy, Maytansinol; 15R-Hydroxy, 3-Ac, Sylphosphate), Peptidolipin NA: Peptidolipin NA. Peptidol Maytansinol: 30-Hydroxy, 3-Ac, Maytansinol; 15R-Hy ipin NA; Val6Peptidolipin NA, 1.6-Phenazinediol, 1.6- droxy, 3-O-(3-methylbutanoyl), Maytansinol: 30-Hydroxy, Phenazinediol; Mono-Meether, 1,6-Phenazinediol; 5-Oxide, 3-O-(3-methylbutanoyl), Maytansinol: 3-O-(3-Hydroxy-3- Phenylalanine dehydrogenase, 1-Phenyl-3-buten-2-ol; (R)- methylbutanoyl), Maytansinol: 3-O-(4-Hydroxy-3-meth form, Phosphatidylethanolamine; Glycerol 2-hexadecanoate ylbutanoyl), Maytansinol: 3-O-(3-Hydroxy-3-methylbu 1-(10R-methyloctadecanoate) 3-phosphoethanolamine, tanoyl), N-de-Me, Maytansinol; 15R-Hydroxy, 3-O-(2- Phospholipase C, 3-Phosphoshikimate 1-carboxyvinyltrans methylpropanoyl), Maytansinol; 15S-Hydroxy, 3-O-(2- ferase, Plectaniaxanthin: (S)-form, 1'-O-B-D-Glucopyrano methylpropanoyl), Maytansinol: 30-Hydroxy, 3-O-(2- side, Plectaniaxanthin: (S)-form, 1'-O-(Hexadecanoyl-f-D- methylpropanoyl), Maytansinol; 15R-Hydroxy,3-propanoyl, glucopyranoside), Polyphosphate glucose Maytansinol: 30-Hydroxy, 3-propanoyl, Maytansinol 3-O- phosphotransferase, Polysaccharide O-methyltransferase, (3-Methylbutanoyl), Maytansinol 3-O-(2-Methylpro Primocarcin, Prodigiosin, Protorifamycin I-M1, Protorifa panoyl), Maytansinol: 3-Propanoyl, MD 011, Megalomicin mycin I-M1; 34a-Deoxy, Pseudouridine C. 3-Me, C-L- A: 3A,4A-Di-Ac, Mercury(II) reductase, Mesenterin, Meta Rhamnopyranosyl-(1->2)-O-L-rhamnopyranosyl-(1->4)-L- cycloprodigiosin, 1-Methyl-3-carboline, Methylcyclodecyl rhamnose, 3-O-O-L-Rhamnopyranosyl-L-rhamnose; prodiginine, Methylene-fatty-acyl-phospholipid synthase, C.-Pyranose-form, Me glycoside, 2-Me, Rhodonocardin A, 4-Methy-3,9,11-hexacosanetriol: 3-Meether, 8-Methylhexa Rhodonocardin A; 12b-O-Deglycosyl, Rifamycin, Rifamy decanoic acid: (S)-form, 10-Methyl-9-hexadecenoic acid, cin; O4-(Carboxymethyl), Rifamycin; 8-Deoxy, O4-(car 11-Methyl-12-octadecenoic acid; (115,12Z)-form, 14-Meth boxymethyl), Rifamycin G. Rifamycin G: 16, 17Z-Didehy ylpentadecanoic acid, Muracein A, Muracein B. Muracein C, dro, Rifamycin P. Rifamycin Q, Rifamycin S; 8-Deoxy, Mutactimycin A; 3 A-O-De-Me, Mutactimycin A; 4A-Me Rifamycin S; 16,17-Dihydro, Rifamycin S; 16,17-Dihydro, ether, Mutactimycin A; Di-O-de-Me, Mycobacteriocin M 12, 17-hydroxy, Rifamycin S; 3.31-Dihydroxy, Rifamycin S; Mycobactin, Mycobactin: Mycobactin T. Mycocyclosin, 3-Hydroxy, Rifamycin S: 30-Hydroxy, Rifamycin S: 3-Hy Mycolactone A, Mycolactone A, 12'-Deoxy, Mycolactone A: droxy, 8-deoxy, Rifamycin verde, Rifamycin W. Rifamycin 4E-Isomer, Mycolactone A: 2-Methyl, Mycolactone F. W: 35-Aldehyde, 35->25-hemiacetal, Rifamycin W: 35-Car

US 2016/01 86168 A1 Jun. 30, 2016

3-pentenoic acid; (R)-form, 2-Amino-1,3-propanediol; N-(2- biotic 165, Antibiotic 1695, Antibiotic 1728, Antibiotic 1762, Hydroxybenzoyl), 2-Amino-1,3-propanediol; N-(2- Antibiotic 1904, Antibiotic 206, Antibiotic 207, Antibiotic Hydroxybenzoyl), 1-Ac, 1-Amino-1,2,3- 216, Antibiotic 2305, Antibiotic 232, Antibiotic 2339, Anti propanetricarboxylic acid: (1S,2S)-form, 1"-Nitrile, biotic 2381, Antibiotic 24010, Antibiotic 2789, Antibiotic 2-Amino-1-propanol: (S)-form, N-(2-Hydroxybenzoyl), 2844-31; Antibiotic 2844-31A, Antibiotic 2844-31; Antibi N-(2-Aminopropanoyl)benzeneacetamide; (S)-form, otic 2844-31B, Antibiotic 2844-31; Antibiotic 2844-3 1C, 3-Amino-2-pyrazinecarboxylic acid; N-Ac, 2-Amino-3-(2- Antibiotic 2911-2, Antibiotic 29119, Antibiotic 2928, Anti pyridinyl)propanoic acid, (S)-form, 3-Amino-3-(2-thiazolyl) biotic 32, Antibiotic 323-58, Antibiotic 362, Antibiotic 3671, propanoic acid, 2-Amino-3-(1H-1,2,4-triazol-3-yl)pro Antibiotic 3738-36, Antibiotic 472, Antibiotic 5, Antibiotic panoic acid: (S)-form, Amipurimycin, Ammosamide B, 5102-2, Antibiotic 5590, Antibiotic 560, Antibiotic 58, Anti Ammosamide B: 2-Thione analogue, Amphomycin, Ampho biotic 583, Antibiotic 6431 36, Antibiotic 661, Antibiotic tericin B, Amphotericin B; 16-Decarboxy, 16.f3-methyl, 6734 21, Antibiotic 69, Antibiotic 713, Antibiotic 741, Anti Amphotericin B; 16-Decarboxy, 16 B-methyl, 8-deoxy, agly biotic 768, Antibiotic 792, Antibiotic 80-258, Antibiotic 878 cone, Amphotericin B; 16-Decarboxy, 16.f3-methyl, 8-deoxy, 6, Antibiotic 9408, Antibiotic 991, Antibiotic A 110-1, Anti 28.29-dihydro, 15-ketone, Amphotericin B; 16-Decarboxy, biotic 116A, Antibiotic 1176A, Antibiotic A 121, Antibiotic 16.f3-methyl, 15-ketone, Amphotericin B; 19-Deglycosyl, 13285A, Antibiotic 14A, Antibiotic A 1502, Antibiotic A 19-O-(4-amino-4,6-dideoxy-B-D-mannopyranoside), 171-2, Antibiotic A 1787, Antibiotic A 19009, Antibiotic A Amphotericin B; 8-Deoxy, Amphotericin B; 8-Deoxy, 28.29 2121, Antibiotic A 2121; Antibiotic A 2121-1, 4DO-Deacyl, dihydro, Amphotericin B; 28.29-Dihydro, Amphotericin B; Antibiotic A 216, Antibiotic A 2201, Antibiotic A 221, Anti 28.29-Dihydro, 15-ketone, Amphotericin B; 28.29-Dihydro, biotic 273a2; Antibiotic 273a2O, Antibiotic 273a2; Antibiotic 7-Oxo, Amphotericin B; 13-Epimer, 13-Meether, Amphoteri 273a2B, Antibiotic A28, Antibiotic A 280, Antibiotic A cin B: 15-Ketone, Amphotericin B; 13-Meether, Amphoteri 33853, Antibiotic A 35512, Antibiotic A 38533, Antibiotic cin B; 7-Oxo, Amycin, Amylostatin, Amylostatin; Amylosta 4181A, Antibiotic A 477, Antibiotic A 4993, Antibiotic A tin B, Amylostatin; Amylostatin C, Amylostatin; Amylostatin 54145, Antibiotic A54145: Antibiotic A54145D. 3"-Deoxy, D. Amylostatin; Amylostatin E, Amylostatin; Amylostatin F. 3-O-de-Me, Antibiotic A 54145: Antibiotic A 54145D, Amylostatin; Amylostatin K, Amylostatin; Amylostatin L. 3-Demethoxy, Antibiotic A 54145: Antibiotic A 54145D, Amylostatin; Amylostatin M, Amylostatin; Amylostatin N. 3-Demethoxy, 3"-deoxy, Antibiotic A 54145; Antibiotic A Amylostatin; Amylostatin XG. Amylostreptin, AN3, AN 5, 54145E, 3-Demethoxy, 3"-deoxy, Antibiotic A54556, Anti AN 7, Anantin, Anantin: Des-Phe analogue, Ancovenin, biotic 549-A1, Antibiotic 593A, Antibiotic A 5945, Antibi Androstane-3,17-dione; 5C-form, Angucyclinone C, Angust otic A 60, Antibiotic A 6067, Antibiotic 67-121A; N-De-Me, mycin A, Anhydromaggiemycin, Anhydromaggiemycin; Antibiotic A74528, Antibiotic A 77951, Antibiotic A80789, 12-Deoxy, Anhydromaggiemycin; 4,12-Dideoxy, Anhydro Antibiotic 859A, Antibiotic 875A, Antibiotic 927A, Antibi maggiemycin; 10-Hydroxy, 4,12-dideoxy, Anhydro-e-pyrro otic A94964, Antibiotic A9594, Antibiotic A 9828, Antibi mycinone, Anhydrotetracycline monooxygenase, Anisomy otic A011A, Antibiotic A 0341A, Antibiotic A 0341A:3-Hy cin; (-)-form, Anisomycin; (-)-form, O-De-Ac, Anisomycin; droxy, Antibiotic A 16886A, Antibiotic A 201A, Antibiotic A (-)-form, O-De-Me, Anisomycin; (-)-form, O-De-Me, O-de 201A; 2B5.3BS-Dihydro. Antibiotic A 201A, 1B O-Deg Ac, Anisomycin; (-)-form, O-De-Ac, 3-propanoyl, Aniso lycosyl, Antibiotic A 201A; 3"-Hydroxy, Antibiotic A 228A, mycin; (-)-form, O-De-Me, 3-propanoyl, O-de-Ac, Aniso Antibiotic A 39183A, Antibiotic A 41030A, Antibiotic A mycin; (-)-form, O-De-Ac, 3-butanoyl, Anisomycin; (-)- 41030A; 22.45-Bis(dechloro), Antibiotic A 41030A: form, O-De-Ac, 3-(3-methylbutanoyl), 3-p-Anisylidene-6- 22-Dechloro, Antibiotic A 41030A; 45-Dechloro, Antibiotic benzylidene-2.5-piperazinedione; (3Z.6Z)-form, 3-p- A 41030A; 22-Dechloro, dibutyl, Antibiotic A 41030A: Anisylidene-6-benzylidene-2.5-piperazinedione; (3Z.6Z)- 11-O-Galactosyl-(1->2)-galactoside, dibutyl, Antibiotic A form, N4-Me, 3-p-Anisylidene-6-benzylidene-2.5- 41030A, 11-O-Galactosyl-(1->2)-galactoside, Antibiotic A piperazinedione; (3Z.6Z)-form, N1,N4-Di-Me, 3-p- 41030A: 011-Sulfate, Antibiotic A 500359A, Antibiotic A Anisylidene-6-benzylidene-2.5-piperazinedione; (3Z.6Z)- 500359A; 2'-O-Carbamoyl, Antibiotic A 500359A; O-De form, 6,7-Dihydro, N4-Me, Annorumin, Ansaetherone, Me, Antibiotic A 500359A: 2"-Deoxy, Antibiotic A51493A, Ansalactam A. Ansathiazin, Ansatrienin B. Ansatrienin B; Antibiotic A 53868A, Antibiotic A 80915A, Antibiotic A N-Deacyl, N-(4-methylpentanoyl), Ansatrienin B: N-Deacyl, 82548A, Antibiotic AB 021, Antibiotic AB 023; Antibiotic N-tigloyl, Ansatrienin B; 23-Deoxy, Ansatrienin B; 1".2"- AB 023A, Antibiotic AB 023; Antibiotic AB 023B, Antibiotic Didehydro, Ansatrienin B; 20-Me ether, Ansatrienin B: 21 AB 041, Antibiotic A 10255B, Antibiotic A 130B, Antibiotic (Methylthio), Ansatrienin B; 19-(Methylthio), 20.23 A 130B, 27-De?glycosyloxy), Antibiotic A 1308; 28-Epimer, quinone. Ansatrienin B; 20.23-Quinone, Ansatrienin B; 27-de(glycosyloxy), Antibiotic AB 161-2, Antibiotic A 20.23-Quinone, N-deacyl, N-(2-methylbutanoyl), Ansatirie 58365B, Antibiotic AB 650, Antibiotic AB 78, Antibiotic A nin B; 20.23-Quinone, N-deacyl, N-(3-methylbutanoyl), 80915B, Antibiotic A80915B; 7-Demethyl, Antibiotic AB Ansatrienin B; 20.23-Quinone, N-deacyl, N-(4-methylpen 3217A, Antibiotic AB 3217A; 13-O-(6-Hydroxy-1-methyl tanoyl), Ansatrienin B; 20.23-Quinone, 1".2"-didehydro, heptanoyl), Antibiotic AB 3217A; 13-O-(4-Methylpen Anslimins, Anthelvencin A: (S)-form, Anthelvencin B, tanoyl), Antibiotic A 10255C, Antibiotic A 21978C, Antibi Anthracidins, Anthracyclinone blue B, Anthracyclinone blue otic A 21978C; Antibiotic A 21978C1, 11-D-Asparagine B; 12-Deoxy, Anthracyclinone 58G, Anthramycin, Anthra analogue, Antibiotic A21978C; Antibiotic A21978C2, 11-D- mycin; 11-Et ether, N3'-Me, Anthramycin; N3'-Me, Anthra Asparagine analogue, Antibiotic A 21978C; Antibiotic A mycin; 11-Meether, N3'-Me, Anthramycin; Stereoisomer(?), 21978C3, 11-D-Asparagine analogue, Antibiotic A39183C, Antibiotic 1004, Antibiotic 1008, Antibiotic 1100-50, Anti Antibiotic A58365C, Antibiotic A 80915C, Antibiotic AD biotic 11-98, Antibiotic 1308, Antibiotic 131-1, Antibiotic 26-1, Antibiotic AD 26-1, 5-O-Carbamoyl. Antibiotic A 144-3, Antibiotic 156, Antibiotic 1579, Antibiotic 1588, Anti 39183D, Antibiotic A80915D, Antibiotic A 10255E, Antibi US 2016/01 86168 A1 Jun. 30, 2016 54 otic A39183E, Antibiotic AE 56, Antibiotic AF 030, Antibi Antibiotic CP 56064, Antibiotic CP 56064; 12,13-Epoxide, otic A 10255F, Antibiotic AF 1231, Antibiotic A 503083F, Antibiotic CP 73064, Antibiotic CP 91243: 30-Hydroxy, Antibiotic A503083F: Meester, Antibiotic AF 7368E, Anti 4A,4B-di-Meether, Antibiotic CRP2504-1, Antibiotic CV 1, biotic A10255G, Antibiotic A80915G, Antibiotic A10255H, Antibiotic 17927D, Antibiotic D 788-10, Antibiotic D 788 Antibiotic AH 272C2, Antibiotic AH 272|B2, Antibiotic AH 10; Meester, Antibiotic DC 102, Antibiotic DC 105, Antibi 758, Antibiotic AI 5662, Antibiotic A 661 I, Antibiotic A otic DC 14, Antibiotic DC 81: (S)-form, Antibiotic DC 79A, 10255J, Antibiotic AJI 9561, Antibiotic AJI 9561; Meester, Antibiotic DC 8118A, Antibiotic DC 8118A: 8-Ketone, Antibiotic AK 164, Antibiotic AM 8402, Antibiotic A Antibiotic DC 38B, Antibiotic DJ 7164, Antibiotic DJ 400B; 39079S-1, Antibiotic ASK 753, Antibiotic AS-N-7A, Antibi Antibiotic DJ 400B1, Antibiotic DJ 400B; Antibiotic DJ otic A 6888X, Antibiotic A6888X; 20-Aldehyde, Antibiotic 400B2, Antibiotic DMCJ 49, Antibiotic 5838-DNI-3, Antibi A 6888X; 20-Aldehyde, 4B-ketone, Antibiotic A 6888X: otic 5923 DNI, Antibiotic 1-81D-1S, Antibiotic DX 27, Anti 4"-Epimer, 20-aldehyde, Antibiotic A4187-4, Antibiotic AZ biotic 289E, Antibiotic E 367, Antibiotic E 76, Antibiotic E SH 29, Antibiotic 011B, Antibiotic B 1000, Antibiotic 210A, Antibiotic ECO 02301, Antibiotic EI 1511-3, Antibi 10381b2, Antibiotic 1401B, Antibiotic 17-41B, Antibiotic otic EI 1511-5, Antibiotic EI 1511–5: Deepoxy, 5R-hydroxy, 24010B1, Antibiotic B 28963, Antibiotic 301B, Antibiotic Antibiotic EI 1625-2, Antibiotic EI 2346, Antibiotic EM 301B: 5-O-Deglycosyl, Antibiotic 301 B: 5-O-Deglycosyl, 2487, Antibiotic EM 98, Antibiotic F 2787, Antibiotic F 40, N4-de-Me, Antibiotic 4181B, Antibiotic 834B1, Antibiotic B Antibiotic F1370A, Antibiotic FA2713, Antibiotic FA 252C, 15565A, Antibiotic B 1625a-410, Antibiotic BA 6903, Anti Antibiotic F1370B, Antibiotic F 10C, Antibiotic FCE 21424, biotic BA 17039A, Antibiotic BA 181314A, Antibiotic B Antibiotic FCE 21424; 1",3'-Di-Me, Antibiotic FCE 21424; 2289An, Antibiotic B 15565B, Antibiotic BE 14106, Antibi 2"-Thioxo analogue, Antibiotic FD 594, Antibiotic FD 891, otic BE 14106; 8-Deoxy, Antibiotic BE 16627, Antibiotic BE Antibiotic FD 891; Stereoisomer (?), Antibiotic FD 892, 19093, Antibiotic BE 22 179, Antibiotic BE 23254, Antibiotic Antibiotic FK 156, Antibiotic FK506 isomer, Antibiotic FK BE 39891, Antibiotic BE 48021, Antibiotic BE 51068, Anti 520 isomer, Antibiotic FL120B', Antibiotic FL 120B'; O-De biotic BE 52211, Antibiotic BE 54017, Antibiotic BE 54476. Ac, 4-O-(2-methylpropanoyl), Antibiotic FL 657B, Antibi Antibiotic BE 55051. Antibiotic BE 67251. Antibiotic BE otic 289FO, Antibiotic FR 112123, Antibiotic FR 32863, 19412A, Antibiotic BE26554A. Antibiotic BE 40665A; 9.9'- Antibiotic FR 33289; (R)-form, Antibiotic FR 3383, Antibi Dichloro, Antibiotic BE 43472A, Antibiotic BE 43472A; otic FR 66979, Antibiotic FR 900012, Antibiotic FR 900109, 4-Deoxy, Antibiotic BE43472A, 4-Deoxy, 8-Meether, Anti Antibiotic FR 900137, Antibiotic FR 900148, Antibiotic FR biotic BE43472A; 8-Meether, Antibiotic BE 52440A, Anti 900336, Antibiotic FR 900452, Antibiotic FR 900452: Dihy biotic BE 52440A; Monoalcohol, Antibiotic BE 54238A, dro (?), Antibiotic FR 900462, Antibiotic FR 900482, Anti Antibiotic BE 54238A, 1C.-Hydroxy. 2'->1-lactone, Antibi biotic FR 900482; 1,79-Tri-Ac, Antibiotic FU 10; 6'-Deoxy, otic BE 24566B; (+)-form, Antibiotic BE 24566B: (-)-form, 6'-amino, Antibiotic G1, Antibiotic G 252, Antibiotic G. 253, Antibiotic BE 24566B: (-)-form, 10,12-Dichloro, 3-Me Antibiotic G 83, Antibiotic GAI, Antibiotic GE 1655, Anti ether, Antibiotic BE 41956B1, Antibiotic BE 41956B1; biotic GE 811 12, Antibiotic GE 37468A, Antibiotic GE 4'-Epimer, Antibiotic BE 52211C, Antibiotic BE 5221 1C: 37468A: 6-N-De(alkylaminoalkyl), Antibiotic GE 37468A: A17-Isomer, Antibiotic BE 45985X, Antibiotic B 1625FA2|B- 3-N-De(carboxyalkyl), Antibiotic GE 3B, Antibiotic GEX 1, Antibiotic B2847OH, Antibiotic BI 32169, Antibiotic BK 103, Antibiotic GP III, Antibiotic 2814H, Antibiotic H3787, 217y, Antibiotic B2847CL. Antibiotic BL 580, Antibiotic BL Antibiotic 3874H3, Antibiotic 3874H4, Antibiotic 3874H5, 617, Antibiotic B1 T20, Antibiotic BU 4726G, Antibiotic C Antibiotic 3874H6, Antibiotic H 668, Antibiotic H 85, Anti 104, Antibiotic C 104; 4A-Deacyl, Antibiotic C 104; 6-Hy biotic HA-1-92, Antibiotic HA-2-91, Antibiotic HHM 15, droxy, Antibiotic C 1051, Antibiotic C 13648, Antibiotic C Antibiotic H 88.111, Antibiotic H 537SY2, Antibiotic I 22, 15462, Antibiotic C 15462; Antibiotic C 15462V, Antibiotic Antibiotic 8510-I. Antibiotic IC 101, Antibiotic IC 101; C2, Antibiotic 202C, Antibiotic C22-4, Antibiotic 301C, N1-Deoxy, Antibiotic IN 183T, Antibiotic IT 62B, Antibiotic Antibiotic C4; 5'-Alcohol, Antibiotic 4018-1C, Antibiotic JA 4015, Antibiotic JA 4495, Antibiotic JBIR 06, Antibiotic 5399C, Antibiotic 6904C, Antibiotic C 8030B, Antibiotic JBIR 06:9-Demethyl, Antibiotic JBIR 11, Antibiotic JBIR CBS 154-94A, Antibiotic CBS 154-94B, Antibiotic CBS 88, Antibiotic JI 20B, Antibiotic K 502, Antibiotic K 502: 154-94B; Me ester, Antibiotic CC 10232, Antibiotic C Antibiotic K 502-7, Antibiotic K 502; Antibiotic K 502A, 8030D, Antibiotic CDA, Antibiotic CDA; Antibiotic CDA Aglycone, Antibiotic K802-4, Antibiotic K97-0239A, Anti 4B, 4',6-Deoxy, 3.3-O-phosphate, Antibiotic CDA; Antibi biotic K252b; 3'-Deoxy, 3'-(methylamino), Meester, Antibi otic CDA 4B, 4,6-Deoxy, 4.6-fluoro, 3.3-O-phosphate, Anti otic K 252b: Meester, Antibiotic K 41B, Antibiotic K 41B: biotic CDA; Antibiotic CDA 4B, 4',6-Deoxy, 4',6-fluoro, 2.1, 15-O-Deglycosyl, 15-Me ether, Antibiotic K 41B: 15-De 3.1-didehydro (Z-), 3.3-O-phosphate, Antibiotic CDK 711A, (glycosyloxy), Antibiotic K97-0239B, Antibiotic KF 77AG6: Antibiotic CDK 711A; 1D-Deglycosyl, Antibiotic CE 108, (S,S)-form, Antibiotic KI26A, Antibiotic KOSN 1633, Anti Antibiotic CE 108; Amide, Antibiotic CE 108: 14-Decar biotic KOSN 1633; 4,5-Dihydro, Antibiotic KT 151, Antibi boxy, 14C-methyl, Antibiotic C 19393E5, Antibiotic CG otic L 11-1, Antibiotic L 156602, Antibiotic L 29-141, Anti 15B, Antibiotic CG 15B; 3B-Deoxy, Antibiotic CG 15B; biotic L 681217, Antibiotic L 72, Antibiotic LA 5352, 3B-Deoxy, N,N-di-Me, Antibiotic CG 15B; 3B-Deoxy, Antibiotic LA 5937, Antibiotic LC 28, Antibiotic LIA 0331, N-Me, Antibiotic CG 15B; 3B, 10-Dideoxy, 135-alcohol, Antibiotic LIA 0735, Antibiotic LIA 0832C, Antibiotic LIA Antibiotic CG 15B; 10-Deoxy, 135-alcohol, Antibiotic CG 0832D, Antibiotic LL-A 491, Antibiotic LL-AB 664, Antibi 15B; 6-Deoxy, N,N-di-Me, Antibiotic CG 15B; N,N-Di-Me, otic LL-AB 664; N5-Me, Antibiotic LL-BH872O, Antibiotic Antibiotic CG 15B; N-Me, Antibiotic CG 17B, Antibiotic CG LL-BH872O: 25-Alcohol, Antibiotic LL-BH872o.: 45-Hy 17B; 38-Deoxy, Antibiotic CG 17B; 3B-Deoxy, 4-Meether, droxy, 25-alcohol, Antibiotic LL-BH 890C., Antibiotic LL Antibiotic CG 17B: 4-Meether, Antibiotic CK 4416, Antibi BH 890?, Antibiotic LL-BL 869B, Antibiotic LL-BM 27B, otic CP 101765, Antibiotic CP 21635, Antibiotic CP 50833, Antibiotic LL-BM 27B; 2-Deoxy, Antibiotic LL-BM 27B; US 2016/01 86168 A1 Jun. 30, 2016

2-Deoxy. 2'-amino, Antibiotic LL-BM 726, Antibiotic LL Antibiotic RK 955A, Antibiotic Ro 09-0766, Antibiotic Ro BO 2964, Antibiotic LL-C08078, Antibiotic LL-D 49.194 B1, 09-0767, Antibiotic Ro 09-0768, Antibiotic 1 1837 RP. Anti Antibiotic LL-D 4919431; 17-Deoxy, 14, 17-epoxide, Anti biotic RP 13252, Antibiotic RP 16511, Antibiotic RP 16978, biotic LL-D 49194 B1; 17-Deoxy, 14,17-epoxide, 4'-O-de Antibiotic RP 17967, Antibiotic RP 18061, Antibiotic RP Ac, Antibiotic M259, Antibiotic M331, Antibiotic M 770, 18887, Antibiotic 19402RP, Antibiotic RP23671, Antibiotic Antibiotic M368A, Antibiotic MA39, Antibiotic MA 144E1, RP 63834, Antibiotic RP 6798, Antibiotic RP 7071, Antibi Antibiotic MA 144 U7, Antibiotic MA 144 U7:4B-Deglyco otic RP 9768, Antibiotic RP 9971, Antibiotic RPI 856A, syl, Antibiotic MA 144 UT; 4B-Deglycosyl, 3B-deoxy, Anti Antibiotic RPI 856A:3"-Epimer, Antibiotic RPI856C, Anti biotic MA 144 U7; 1,2CR-Dihydroxy, 4C-ketone, 3A-O- biotic RPI 856C; 3"-Epimer, Antibiotic RS 10, Antibiotic S carbamoyl, Antibiotic MA 144 UT; 4C-Epimer, 3B-deoxy, 19, Antibiotic S 383-0, Antibiotic S 433, Antibiotic S 541; Antibiotic MA 144 UT; 4C-Epimer, 11-hydroxy, 3 A.3B Antibiotic S 541A, Antibiotic S 541; Antibiotic S 541A, dideoxy, Antibiotic MA 144 UT; 4C-Epimer, 1-hydroxy, 5-Ketone, Antibiotic S 541; Antibiotic S 541A, 7-Deoxy, 3A.3B-dideoxy, Antibiotic MA 144 UT; 4C-Epimer, 1-hy 2,5,6,7-tetradehydro, Antibiotic S 541; Antibiotic S 541A, droxy, 3B-deoxy, Antibiotic MA 144 U7; 4C-Ketone, Anti A2-Isomer, Antibiotic S 541; Antibiotic S 541A, O5-Me, biotic MA 144 UT; 1-Hydroxy, 3A-deoxy, 4C-ketone, Anti Antibiotic S541; Antibiotic S541C, Antibiotic S541; Anti biotic MA 144 U7: 1-Hydroxy, 4C-ketone, Antibiotic M biotic S541C, O5-Me, Antibiotic S541; Antibiotic S541D, 3688, Antibiotic MC 637SY1, Antibiotic MC 696-SY2B, Antibiotic S 541; Antibiotic S 541D, O5-Me, Antibiotic S Antibiotic MD 129C2, Antibiotic ME 168, Antibiotic MF 685, Antibiotic S 728, Antibiotic SA16-10, Antibiotic SA 722-02, Antibiotic MF-EA 705C., Antibiotic MF-EA 705C.: 1795, Antibiotic SA5-10, Antibiotic SAB 711, Antibiotic (1"Z)-Isomer, 3",4'-dihydro, Antibiotic MH 850, Antibiotic SAX 10, Antibiotic SB 212305, Antibiotic SB 217452, Anti MH 563-32F1, Antibiotic ML 449, Antibiotic MM 44785, biotic SB 22484, Antibiotic S 583B, Antibiotic S8878, Anti Antibiotic MM 44786, Antibiotic MM 44787, Antibiotic MM biotic SBR 22, Antibiotic S-4C 33, Antibiotic S 632C, Anti 44788, Antibiotic MM 8, Antibiotic MR 387A, Antibiotic biotic S 3907C4B, Antibiotic S 3907C4B; 4'-O-Sulfate, MR 387A: 4-Deoxy, Antibiotic MS 282, Antibiotic MSO Antibiotic Sch 212394, Antibiotic Sch 382582, Antibiotic 901809, Antibiotic MT 10, Antibiotic MYC 8005, Antibiotic Sch 382582: De(methylthio), Antibiotic Sch. 47555, Antibi NA 181, Antibiotic N44A-21, Antibiotic NA 699, Antibiotic otic Sch. 47555; 2.3"-Didehydro, 4"-ketone, Antibiotic Sch NA 22598A, Antibiotic NA 22598A1, Antibiotic NAT 13, 538415, Antibiotic Sch. 58450, Antibiotic SEN 143, Antibi Antibiotic NC-GAI, Antibiotic NK 1012-2, Antibiotic NK otic SEN 315, Antibiotic SEN 366D1, Antibiotic SEN 1012-3, Antibiotic NK 86-0186, Antibiotic NK 30424A, 366D1, 2,3-Dihydro, Antibiotic SEN 366D1: 2-Hydroxy, Antibiotic NK 30424A; Stereoisomer, Antibiotic NK 2,3-dihydro, Antibiotic SEN 366F, Antibiotic SF 1130, Anti 170204B, Antibiotic NP522, Antibiotic NRC 101, Antibiotic biotic SF 1195, Antibiotic SF 1223, Antibiotic SF 1508, Anti NRC 501, Antibiotic NRC-C7, Antibiotic NRCS 15, Antibi biotic SF 1623, Antibiotic SF 1739, Antibiotic SF 1771, Anti otic NS 5, Antibiotic NS 5; N-Ac, Antibiotic NS 5; 1,2'- biotic SF 1774, Antibiotic SF 1902; Antibiotic SF 1902A1, Didehydro, N—Ac, Antibiotic NSC-C, Antibiotic Antibiotic SF 1902; Antibiotic SF 1902A2, Antibiotic SF N05 WA963 A, Antibiotic N05 WA963A; 4A-Deglycosyl, 1902; Antibiotic SF 1902A3, Antibiotic SF 1902; Antibiotic Antibiotic N05 WA963A: 2C,3C-Didehydro, Antibiotic NW SF 1902A5, Antibiotic SF 1902; Antibiotic SF 1902A4a, G01, Antibiotic NW-G01: 2",3"-Didehydro, Antibiotic O Antibiotic SF 1902; Antibiotic SF 1902A4b, Antibiotic SF 2867C., Antibiotic OA 7653, Antibiotic OA 612981, Antibi 1999, Antibiotic SF 2012, Antibiotic SF 2059, Antibiotic SF otic OA612981: 8-Deoxy, Antibiotic OA6129B1: 6-Epimer, 2068, Antibiotic SF 2077, Antibiotic SF 2330, Antibiotic SF Antibiotic OA 6129B 1: 8-O-Sulfate, Antibiotic OA 6129D, 2354, Antibiotic SF 2398, Antibiotic SF 2425, Antibiotic SF Antibiotic OA 6129E, Antibiotic O 611B, Antibiotic OS 2437, Antibiotic SF 2543, Antibiotic SF 2547, Antibiotic SF 1804, Antibiotic OS 3256B, Antibiotic P 125, Antibiotic P 2575, Antibiotic SF 2575; 4'-O-Deacyl, 4'-O-(2-ethyl-2Z 15149, Antibiotic P 15149; 8,19-Didehydro, 8, 19-epoxide, butenoyl), Antibiotic SF 2575: 12a-O-De-Me, Antibiotic SF Antibiotic P 15149; 12-Hydroxy, Antibiotic P 15149; 8-Hy 2609, Antibiotic SF 2716, Antibiotic SF 2768, Antibiotic SF droxy, Antibiotic 1645 P1, Antibiotic 1645P2, Antibiotic 2771, Antibiotic SF 2776, Antibiotic SF 701, Antibiotic SF 31668P, Antibiotic P 371; Antibiotic P 371 A1, Antibiotic P 701: N2"-De-Me, N5-Me, Antibiotic SF 701; N2"-Me, Anti 371; Antibiotic P371A1, 4,3-Acetoxy, Antibiotic P371; Anti biotic SF 98, Antibiotic SF 1540A, Antibiotic SF 1670A, biotic P 371 B1, Antibiotic P 371; Antibiotic P 371 B2, Anti Antibiotic SF 1961A, Antibiotic SF 2050A, Antibiotic SF biotic P 6226, Antibiotic PA 108, Antibiotic PA 128, Antibi 2111A, Antibiotic SF 2415A1, Antibiotic SF 2415A2, Anti otic PA 150, Antibiotic PA 153, Antibiotic PA 166, Antibiotic biotic SF 2415A3, Antibiotic SF 2415A3: 7-Demethyl, Anti PA 616, Antibiotic PA 86, Antibiotic PA 133A, Antibiotic PA biotic SF 2446A1. Antibiotic SF 2446A1, Aglycone, Antibi 46101A, Antibiotic PA 46101A: O6-(2,4-Di-O-methyl-3-C- otic SF 2446A1: 6-Deoxy, Antibiotic SF 2446A1; 1'-Epimer, methyl-O-rhamnopyranoside), Antibiotic PA 133B, Antibi Antibiotic SF 2446A1; 1'-Epimer, 6-deoxy, Antibiotic SF otic PA 155B, Antibiotic PA 32413-I, Antibiotic PD 116152, 1306B, Antibiotic SF 1540B, Antibiotic SF 1961B, Antibi Antibiotic PD 116740, Antibiotic PD 116740; O-De-Me, otic SF 2103B, Antibiotic SF 2111B, Antibiotic SF 2415B1, 6-O-(2,3,6-trideoxy-O-L-threo-hexopyranoside), Antibiotic Antibiotic SF 2415B2, Antibiotic SF 24.1583, Antibiotic SF PD 118576, Antibiotic PD 118576A1, Antibiotic PD 689B, Antibiotic SF 2587C, Antibiotic SF 733C, Antibiotic 118576A1; 19-Me ether, Antibiotic PD 118576A2, Antibi SF 2012L, Antibiotic SH 50, Antibiotic SK 229, Antibiotic S otic PDE I, Antibiotic PDE II, Antibiotic PI 080, Antibiotic PI 213L, Antibiotic SOB 7, Antibiotic SP 351. Antibiotic SR 080; 3-O-Deglycosyl, Antibiotic PI 080: 3-O-Deglycosyl, 1223, Antibiotic SR 1768C, Antibiotic SR 1768F, Antibiotic 2C,3C-dihydro, Antibiotic PI 085, Antibiotic PI 087, Antibi SR 1768G, Antibiotic SS 33410, Antibiotic SS 49, Antibiotic otic PS 6, Antibiotic PS 8, Antibiotic 3543 R1, Antibiotic R SS 70, Antibiotic SS 21020A, Antibiotic SS 5401A, Antibi 906, Antibiotic RES 701, Antibiotic RK 1441A, Antibiotic otic SS 56A, Antibiotic SS 56A: 4'-Epimer, Antibiotic SS RK 1441A; 11-Ketone, 3-O-de-Me, Antibiotic RK 699A, 8215A, Antibiotic SS 288B, Antibiotic SS 288B; 1,3B,3C,

US 2016/01 86168 A1 Jun. 30, 2016

4,13-di-Ac, 8-Ethyl-1,6,10,11-tetrahydroxy-5,12-naph 5-Deoxy, 6'-N-Et, 1-N-(aminoacetyl). Fortimicin KE: thacenedione; 7-Deoxy, 4-Meether, 135-acetoxy, 3-Ethyl-1, 5-Deoxy, 6'-N-Et, 1-N-(formylaminoacetyl), Fortimicin KE: 6.8-trihydroxybenzalanthracene-7,12-dione, 3-Ethyl-1,6,8- 5-Deoxy, 6'-N-Me, Fortimicin KE: 5-Deoxy, 6'-N-Me, 1-N- trihydroxybenzalanthracene-7,12-dione; 13, 14-Didehydro, (aminoacetyl), Fortimicin KE: 5-Deoxy, 6'-N-Me, 1-N- 3-Ethyl-1,7,8-trihydroxybenzaanthracene-5,6-dione, (aminocarbonyl)aminoacetyl. Fortimicin KE: 5-Deoxy, 8-Ethyl-1,6,11-trihydroxy-5,12-naphthacenedione, 8-Ethyl 6'-N-Me, 1-N-(formylaminoacetyl). Fortimicin KE: 1,6,11-trihydroxy-5,12-naphthacenedione: 1-Me ether, 5-Deoxy, 6'-N-Me, 1-N-(iminomethyl)aminoacetyl. 4(15).7(11)-Eudesmadiene-8,9-diol; (8f3.9B)-form, 4(15).7 Fortimicin KE: 6-Epimer, 5-deoxy, Fortimicin KE: 4-Epimer, (11)-Eudesmadien-9-ol; 93-form, Eulicin, Eurocidin T. 5-deoxy, 6'-N-Me, Fortimicin KE: 6-Epimer, 5-deoxy, 6'-N- Eurotin A, Eurystatin: Eurystatin A, Eurystatin: Eurystatin B, Me, Fortimicin KE: 4-Epimer, 5-deoxy, 6'-N-Me, 1-N-(ami Eurystatin: Eurystatin C, Eurystatin: Eurystatin D, Eurysta noacetyl), Fortimicin KE: 4-Epimer, 5-deoxy, 6'-N-Me, 1-N- tin; Eurystatin E, Eurystatin; Eurystatin F. Evericin, Exfolia (formylaminoacetyl). Fortimicin KE: 6-Epimer, 5-deoxy, mycin, Exfoliamycin; 3-Deoxy, 3,4-didehydro, Exfoliamy 6'-N-Me, 1-N-(formylaminoacetyl). Fortimicin KE: cin: 3-Me ether, Exfoliatin, Ezomycin A1, Ezomycin A2, 4-Epimer, 5-deoxy, 6'-N-Me, 1-N-(iminomethyl)amino Ezomycin B1, Ezomycin B1; 1-Epimer, Ezomycin B2, Ezo acetyl. Fortimicin KE: Stereoisomer, Fosfazinomycin A, mycin B2: 1-Epimer, Ezomycin D1, Ezomycin D2, FA 1819, Fosfazinomycin B, Fostriecin, Fostriecin; 13-Deoxy, Fostrie Factumycin, Factumycin; 14E-Isomer, Factumycin; 14E-Iso cin; O-Dephospho, Fostriecin; 5S-Hydroxy, Fostriecin: mer, 5,6-dihydro, Factumycin; 14E-Isomer, 29-Me ether, 5S-Hydroxy, O-dephospho, Fostriecin; Parent hydroxyacid, Farinamycin, Fattiviracin A1, Fattiviracins, FCRC 53, Feg 5S-hydroxy, FR 182876, FR 182877, Fradicin, Fredericamy lymycin, Feigrisolide A, Feigrisolide A: 8-Epimer, Fei cin A, Fredericamycin B, Fredericamycin C, Fredericamycin grisolide A: 8-Epimer, 3-deoxy, 2,3-didehydro, Feigrisolide C1, Fredericamycin E, Fredericamycin M1, Fredericamycin C. Feigrisolide C; Stereoisomer (?), Feigrisolide D, Feldamy M1; 9,12-Quinone, Fredericamycin M1; 9,12-Quinone, cin, Fermicidin, Ferramidochloromycin, Ferrimycin A1, Fer 14-hydroxy, Fredericamycin M3, Fredericamycin M4, Fre rimycin A2, Ferrioxamine A2, Ferrioxamine B, Ferrioxamine dericamycin MS, Frenolicin, Frenolicin; Deepoxy, 4a, 10a D2, Ferromycin, Ferropyrumycin, Ferroverdin, Ferroverdin; didehydro, 4B-hydroxy, Me ester, Frenolicin; Deepoxy, 8-Monocarboxy(Z-), Ferroverdin; 8-Monohydroxy(E-), 4a, 10a-didehydro, Frenolicin B, Frenolicin B: 5a,11a-Ep Feruloyl esterase, Feudomycin B, Feudomycin B; O-De-Me, oxide, Fridamycin E; (R)-form, Frigocyclinone, Friulimicin; Feudomycin C, Feudomycin C. Aglycone, Feudomycin C: Friulimicin A, 4'-Parent acid, Friulimicin; Friulimicin B, De(glycosyloxy), Feudomycin C; 10B-Hydroxy, Feudomy 4'-Parent acid, Friulimicin; Friulimicin D, 4'-Parent acid, cin C; 10B-Hydroxy, aglycone, Fibrostatins, Ficellomycin, Fructan B-(2,6)-fructosidase, 2,6-B-Fructan 6-levanbiohy Filipin; Filipin I, Filipin; Filipin II, Filipin; Filipin III, Filipin; drolase, Fuchurmycin B, Fucothricin, Fujianmycin A, Filipin III, 3- or 1'-Epimer, Flavacid, Flavensomycin, Flaveo Fujianmycin A: 4-Epimer, 8-Me ether, Fujianmycin A; lin, Flavofungin: Flavofungin I. Flavofungin: Flavofungin I. 13-Hydroxy, 8-Me ether, Fujianmycin A; 8-Me ether, Fuji Stereoisomer, Flavofungin: Flavofungin I, 14-Demethyl, mycin, Fujimycin; 95-Alcohol, Fujimycin; 31-O-De-Me, 19,21-diepimer, Flavofungin: Flavofungin I, 28.29-Dihydro, Fujimycin; 31-O-De-Me, 31-ketone, Fujimycin; 25-Dem 23-deoxy. 24.29-dihydroxy, Flavofungin: Flavofungin II, ethyl, Fujimycin; 9-Deoxo, 31-O-de-Me, Fujimycin; 2',3'- Flavofungin: Flavofungin II, Stereoisomer, Flavopentin, Fla Dihydro, Fujimycin; Lower homologue, Fulvomycin, Fuma voviridomycin, Flavucidin, Flazine: Meester, Fluorin, Fluo nomycin, Fungichromatin, Fungichromin, Fungichromin: roacetaldehyde, Fluoroacetic acid, Fluorothreonine transal 32-Deethyl, 30-methyl, stereoisomer, Fungichromin: dolase, Fluostatin A. Fluostatin A; 2,3-Dihydro, 3R-chloro, 33-Demethyl, stereoisomer, Fungichromin; Stereoisomer, 2S-hydroxy, 1 R-alcohol, Fluostatin A; 2,3-Dihydro, 2-hy 2.4-Furandicarboxylic acid; Di-Meester, 2.5-Furandimetha droxy, 15-alcohol, Fluostatin A; 2S,3S-Epoxide, 1 R-alcohol, nol, 2.5-Furandimethanol; Di-Ac, 2.5-Furandimethanol: Fluostatin A; 2S,3S-Epoxide, 1 R-alcohol, 1-O-(2-methyl Mono-Ac, 2-Furanol; OH-form, Ac. Furanomycin, Furanon propanoyl), Fluvirucin B; Fluvirucin B3, 4'-Epimer, Fogacin, aphthoduinone I. Furanonaphthoguinone I: O-De-Me, Fura Formadicins; Formadicin A, Formadicins; Formadicin C, nonaphthoduinone I: 6-Demethyl. Furaquinocin G, Formycin A, Formycin B, 3-(4-Formylphenyl)amino-4,7- Furaquinocin H. Furaquinocin H; 5'-Deoxy, Furaquinocin H: dihydroxy-5-octenoic acid; Meester, Foromacidin A, Foro 6'-Deoxy, Furaquinocin H; 6'-Deoxy, 5'-carboxylic acid, macidin A: 3-Ac, Foromacidin A; 4A,9-Dideglycosyl, Furaquinocin H; 6'-Deoxy, 5'-carboxylic acid, amide, 18-deoxo. 9-ketone, 3-propanoyl, Foromacidin A; 4A,9- Furaquinocin H. 1",6'-Dideoxy, Furaquinocin H; 5'6'- Dideglycosyl, 18-deoxo, 3-propanoyl. Foromacidin A Agly Dideoxy, Furaquinocin H. 1",6'-Dideoxy, 1,2-didehydro(E-), cone, 18-deoxo, Foromacidin A; Aglycone, 18-deoxo, 9-ke Furaquinocin H; 1',5',6'-Trideoxy, Futalosine, Futalosine tone, Foromacidin A; 18-Alcohol, Foromacidin A; hydrolase, Galactan 1,3-B-galactosidase, Galbonolide A, 4B-Butanoyl, 3-Ac, Foromacidin A, 4B-Butanoyl 3-pro Galbonolide B, Galbonolide C, Galbonolide D, Galirubin A, panoyl, Foromacidin A 3.4B-Di-Ac, Foromacidin A; 3.4B Galtamycinone; 4'-O-(2E,4E-Decadienoyl), Galtamycinone; Dipropanoyl, Foromacidin A; 4B O-(3-Methylbutanoyl), 3'-O-2,6-Dideoxy-3-D-arabino-hexopyranosyl-(1->4)-2,3, Foromacidin A; 4B O-(3-Methylbutanoyl), 3-Ac, Foroma 6-trideoxy-C-D-threo-hexopyranoside. Galtamycinone; cidin A; 4B O-(3-Methylbutanoyl), 3-propanoyl, Foroma 3'-O-(2,3,6-Trideoxy-C-D-threo-hexopyranoside), Galtamy cidin A; 4B O-(2-Methylpropanoyl), 3-Ac, Foromacidin A cinone; 3'-O-2,3,6-Trideoxy-O-L-lyxo-hexopyranosyl-(1- 4B O-(2-Methylpropanoyl), 3-propanoyl, Foromacidin A; >3)-2,6-dideoxy-f-D-arabino-hexopyranosyl-(1->4)-2,3,6- 4B-Propanoyl, 3-Ac, Foromacidin A; 18-Deoxo, Foromaci trideoxy-C-L-lyxo-hexopyranosyl, Gancidin, din A; 17-Methylene, Foromacidin A: 3-Propanoyl, Foroma Ganefromycin 81, Ganefromycin 81; 32-Deoxy, Ganefromy cidin A: 3-Propanoyl, 4B Ac, Foromacidin D. Foroxymith cin 81; 32-Deoxy, 13-Meether, Ganefromycin 81; 32-Deoxy, ine, Fortimicin B: 4-Epimer, 1-N-(iminomethyl)amino 13-Meether, 23-O-(phenylacetyl), Ganefromycin 81; 23.32 acetyl. Fortimicin KE: 5-Deoxy, 6'-N-Et, Fortimicin KE: Dideoxy, Ganefromycin 61; 32-O-(2,6-Dideoxy-O-L-galac US 2016/01 86168 A1 Jun. 30, 2016 66 topyranoside), Ganefromycin 81; 23.32-Dideoxy, 13-Me Gombapyrone A; 20-Deoxy, Gombapyrone A; 20-Deoxy, ether, Ganefromycin 81; 21-Epimer, 23.32-dideoxy, Gane O-de-Me, Gombapyrone A. Lower homologue (R=H), fromycin 61; 21-Epimer, 23.32-dideoxy, 13-Meether, Gane 20-deoxy, Gostatin, Gougerotin, Gougeroxymycin, Granato fromycin 81; 13-Me ether, Ganefromycin 81; 13-Me ether, mycin D. Granatomycin D; 3-Epimer, Granatomycin D; 32-O-(2,6-dideoxy-O-L-galactopyranoside), Ganefromycin 4-Hydroxy, Granatomycin D: 4-Hydroxy, 1->4-lactone, 81; 13-Meether, 23-O-(phenylacetyl),32-O-(2,6-dideoxy-C.- Granatomycin D; 4.3-Hydroxy, 1->4-lactone, 19-O-(2,3,6- L-galactopyranoside), Ganefromycin 81; 13-Meether, 24-O- trideoxy-B-D-threo-hexopyranoside), Granatomycin D; (phenylacetyl), 32-O-(2,6-dideoxy-C-L-galactopyranoside), 4?-Hydroxy, 1->4-lactone, 19-O-(2,3,6-trideoxy-C-L-threo Ganefromycin 61; 23-O-(Phenylacetyl), 32-O-(2,6-dideoxy hexopyranoside), Granatomycin D: 4-Hydroxy, Me ester, C-L-galactopyranoside), Ganefromycin 61; 24-O-(Pheny Granatomycin D: 4-Hydroxy. 19-O-(2,3,6-trideoxy-f-D- lacetyl), 32-O-(2,6-dideoxy-O-L-galactopyranoside), Gang threo-hexopyranoside), Granatomycin D; Me ester, Granato tokmycin, Gannibamycin, Garlandosus, Gastric juice mycin D; 19-O-(2,3,6-Trideoxy-L-threo-hexopyranoside), inhibitory substance, Gaudimycin B. Gaudimycin B; Grecocycline A, Grecocycline A; Deepoxy, 6af3-mercapto, 6-Deoxy, Gaudimycin B; 6-Epimer, Gelbecidin, Geldanamy 12af3-hydroxy, Grecocycline C, Grecoketide A, Grecoketide cin, Geldanamycin; 19-(2-Aminoacetyloxy), 4.5-dihydro, A, 4A,5A-Diepimer, Grecomycin, Grisamine, Griselimycin, Geldanamycin; 19-(2-Aminoacetyloxy), 4.5-dihydro, decar Griseobactin, Griseochelin, Griseochelin; 24.25-Didehydro, bamoyl, Geldanamycin; Decarbamoyl, Geldanamycin; Griseococcin D. Griseolic acid, Griseolic acid; 7"-Deoxy, 17-O-De-Me, Geldanamycin; 17-Demethoxy, 17-C-formyl, Griseolic acid; 4'C,5-Dihydro, 7'-deoxy, Griseomycin, 18.21-hydroquinone, Geldanamycin; 17-Demethoxy, 17-C- Griseophagin, Griseorhodin A, Griseorhodin A2, Griseorho formyl, 18.21-hydroquinone, 011-Me, Geldanamycin; din B. Griseorhodin C, Griseorhodin C: 4-Deoxy, Griseorho 17-Demethoxy, 17-hydroxymethyl, Geldanamycin; 8-Dem din C: 3,4-Dideoxy, Griseorhodin C: 4-Meether, Griseorho ethyl, Geldanamycin; 8-Demethyl, 4R*.5S*-epoxide, din K, Griseorhodin L. Griseoviridin, Griseoviridin; Geldanamycin; 4,5-Dihydro, Geldanamycin; 4,5-Dihydro, 20-Deoxy, A20. A22-isomer, 245-methoxy, Griseoviridin; decarbamoyl, Geldanamycin; 4,5-Dihydro, 17-O-de-Me, O20-Me, Griseusin B: (-)-form, Griseusin B: (-)-form, decarbamoyl, Geldanamycin; 18.21-Hydroquinone, 4C-Hydroxy, lactone, Griseusin B: (-)-form, 4C.-Hydroxy, Geldanamycin; 15R-Hydroxy, Geldanamycin; 15R-Hy lactone, O-de-Ac, Griseusin B; (+)-form, 4-Hydroxy, lac droxy. 4,5-dihydro, Geldanamycin; 19-(Methylthio), tone, 3'-O-O-D-2,3,4,6-tetradeoxy-4-(dimethylamino)- Geldanamycin; 19-(Methylthio), 4.5-dihydro, Geminimycin, erythro-hexopyranoside, Grisonomycin, Grividomycin I. Geomycin, Geosmin, Gephyromycin, 2-Geranyl-3,5,7-trihy Grividomycin I: Diastereoisomer, Grixazone B. Grixazone droxy-6-methyl-1,4-naphthoquinone, 2-Geranyl-3,5,7-trihy B; 1'-Aldehyde, GTP diphosphokinase, Guadinomic acid, droxy-6-methyl-1,4-naphthoquinone; 3-Deoxy. 25.35-ep Guadinomine A, Guadinomine A, 1'-Deoxy, Guadinomine A. oxide, Gerfelin; 3'-Me ether, Me ester, 1(10).5- 1'-Deoxy, NTAc, Guadinomine C1, Guadinomine C1; Germacradiene-2,11-diol: (1 (10).E.2C.5E)-form, 1 (10).5- 3'-Epimer, Gualamycin, Guamycin, Guanamycin, 1D-1- Germacradiene-3,11-diol: (1 (10).E.3 (3.5E)-form, 1 (10).5- Guanidino-3-amino-1,3-dideoxy-Scyllo-inositol transami Germacradien-11-ol: (1 (10).E.4S.5E,7R)-form, Gerobriecin, nase, Guanidinodeoxy-Scyllo-inositol-4-phosphatase, Gibbestatin A, Gibbestatin B. Gibbestatin B: 2-Hydroxyphe Guanidolide A, Guanidyl funginA, Guanidylfungin A; N-De nyl ester, Gilvocarcin M. Gilvocarcin M: 6-Alcohol, Gilvo Me, Guanidylfungin A; Meether, Guanine; N7-Oxide, Gut carcin M: 4-Hydroxy, Gilvocarcin V. Gilvocarcin V: Agly ingimycin, Hachimycin, Hachimycin; Trichomycin A, cone, Gilvocarcin V: Aglycone, 6-alcohol, Gilvocarcin V: 5-Deoxy, 9-hydroxy, Haim, Halawanone A, Halawanone B, Aglycone, 12-O-de-Me, Gilvocarcin V: 6-Alcohol, Gilvocar Halichoblelide, Halichomycin, Halstoctacosanolide A, Hal cin V: 1".2"-Dihydro, Gilvocarcin V: 4-Hydroxy, Gilvocar stoctacosanolide A, 4-Deoxo, Halstoctacosanolide A: cin V: 4-Hydroxy. 1",2'-dihydro, Glaciapyrrole A, Glaciapy 4-Deoxo, 32-deoxy, Hamycin X, Harimycin, Hatomarubigin rrole B, Glaciapyrrole C, Globerin, Globismycin, C, Hatomarubigin C; O-De-Me, Hatomarubigin C: Globopeptin, Globoroseomycin, Glomecidin, Glucan endo 11-Deoxy, 6-hydroxy, 1-ketone, Hatomarubigin C: 1-Ketone. 1.3-D-glucosidase, Glucan endo-1,3-O-glucosidase, Glucan HatomarubiginD, Helvolic acid, Helvomycin, Heptaene 757, endo-1,6-B-glucosidase, Glucolipsins; Glucolipsin A, Gluco Heptafungin A, Heptamycin, Heptamycin B, Heptamycin B; mycin, Gluconimycin, 6-O-O-D-Glucopyranosyl-D-glucose, N-De-Ac, N-propanoyl, Heptamycin B; 4"-Hydroxy, Hepta Glucose 1-phosphate guanylyltransferase, Glucose 1-phos mycin B; Ring-opened form, Heptamycin B; Ring-opened phate thymidylyltransferase, Glutamate dehydrogenases; form, N-de-Ac, N-propanoyl, 1-Heptyl-3-hydroxy-2-me Glutamate dehydrogenase (NADP(+)), Glutamate dehydro thyl-9H-carbazole, 3-Heptyl-5-methyl-2(5H)-furanone: (S)- genases; L-Glutamate oxidase, Glutamine Scyllo-inositol form, Herboxidiene, Herboxidiene; 17-O-De-Me, Herboxi transaminase, Glycerinopyrin, Glycerol 1-alkanoates; Glyc diene; 12-Hydroxy, Herboxidiene; 21-Hydroxy, erol 1-(18-methyleicosanoate) Glycerol 1-alkanoates; Glyc Herboxidiene; 5-Hydroxy, Hernandaline: (S)-form, 2'-Alco erol 1-(16-methylheptadecanoate), Glycerol 1-alkanoates: hol, Heronamide A, Heronamide B, Heronamide C, Hexacy Glycerol 1-(15-methylhexadecanoate), Glycerol 1-al clinic acid, Hexaene 80, Hexahydro-7a-hydroxy-3H-pyr kanoates; Glycerol 1-(18-methylnonadecanoate), Glycerol rolizin-3-one; (E)-form, Hexahydro-7a-hydroxy-3H 1-alkanoates; Glycerol 1-(16-methyloctadecanoate), Glyc pyrrolizin-3-one; (+)-form, Me ether, Hexahydro-7a erol 1-alkanoates; Glycerol 1-(17-methyloctadecanoate), hydroxy-3H-pyrrolizin-3-one; (+)-form, (1-Ethoxyethyl) Glycerol 1-alkanoates; Glycerol 1-(14-methylpentade ether, 4.4a,8,9,10,12b-Hexahydro-4a,7,8,12,12b-pentahy canoate), Glycerol 1-alkanoates; Glycerol 1-(12S-methyltet droxy-3-methylbenzaanthracene-1,11-dione, 3.4.4a.5, radecanoate), Glycerol 1,3-dialkanoates; Glycerol 1(3)-(14. 10, 10a-Hexahydro-4a,9,10a-trihydroxy-1-methyl-5,10-di 16-dimethyloctadecanoate)-3(1)–(9E.12E oxo-1H-naphtho2.3-cpyran-3-acetic acid; Meester, 3.3'4, octadecadienoate), Glycinocin, Glycinocin A, Glycopeptide 4.7".9-Hexahydroxy-7.9'-epoxylignan; (7S,7S,8R,8S)- Cl-N-acetylgalactosaminidase, Goadsporin, Gombapyrone A, form, 7'-Ketone, 3.4:3',4'-bis(methylene) ether, 1.3.4.10.11,

US 2016/01 86168 A1 Jun. 30, 2016

cin reductase, C.-OXO-3-cyclohexene-1-acetic acid; (R)-form, Pentalenene, Pentalenic acid, Pentalenic acid; 1-Deoxy, Pen C.-Oxo-3-cyclohexene-1-acetic acid; (R)-form, C.-Alcohol, talenic acid; 1-Deoxy, B-D-glucopyranosyl ester, Pentaleno 9-Oxo-2,4,5,7-decatetraenoic acid, Oxohygrolidin, 4-Oxo-2- lactone, Pentalenolactone A, Pentalenolactone B, Pentaleno nonenoic acid; (E)-form, 7-Oxo-4-oxa-1-azabicyclo[3.2.0) lactone D, Pentalenolactone E. Pentalenolactone F. heptane-3-carboxylic acid; (3R,5S)-form, 2-Oxo-3-phospho Pentalenolactone F. 9-Epimer, Pentalenolactone F: 1C.-Hy nopropanoic acid, Oxopropaline D; (R)-form, Oxopropaline droxy, Pentalenolactone F: 1-Oxo, Pentalenolactone I, Pen D; (R)-form,2'-O-O-L-Rhamnopyranoside, Oxopropaline D; talenolactone O, Pentalenolactone P. Pentopyranine A, Pen (R)-form, 3'-O-O-L-Rhamnopyranoside, Oxopropaline D; topyranine A; 4'-Epimer, Pentopyranine C, Pentopyramine C: (R)-form, 2-Deoxy, Oxopropaline D; (R)-form, 2'-Deoxy, 4'-Epimer, Pentostatin, 2-Pentylpyridine, Pepstanone A, Pep 3-O-O-L-rhamnopyranoside, 4-OXo-2-propyl-4H-benzopy stanone A; N1-Deacyl, N1-hexanoyl, Pepstanone A: ran-5-acetic acid, Oxytetracycline, Oxytetracycline; N1-Deacyl, N1-(4-methylpentanoyl), Pepstatins: Pepsidin A, 7-Chloro, Oxytetracycline; N-De-Me, N-Et, Ozemycin A, Pepstatins: Pepstatin A, Pepstatins: Pepstatin A, Me ester, Ozemycin B, Ozemycin C, Pacidamycin 1, Pacidamycin 2, Pepstatins: Pepstatin A. Hydroxy, Pepstatins: Pepstatin AC, Pacidamycin 3, Pacidamycin 4, Pacidamycin 5, Pacidamycin Pepstatins: Pepstatin B. Pepstatins: Pepstatin BU, Pepstatins: 6, Pacidamycin 7, Pacidamycin D. Pacidamycin 4N, Pacida Pepstatin C, Pepstatins: Pepstatin D. Pepstatins: Pepstatin E, mycin 5T, Pactamycate, Pactamycate; 8"-Hydroxy, Pactamy Pepstatins: Pepstatin F. Pepstatins: Pepstatin G. Pepstatins: cin, Pactamycin; 7-Deoxy, Pactamycin; 5"-Fluoro, Pactamy Pepstatin H. Pepstatins: Pepstatin I, Pepstatins: Pepstatin J, cin; 8"-Hydroxy, Pactamycin; 2'-Me ether, Padanamide B, Pepstatins: Pepstatin PR, Pepthiomycin, Pepticinnamin, Pep Paim, Paldimycin; Paldimycin A, Paldimycin; Paldimycin tide AN 2, Peptide P3A, Peptimycin, Perimycin A, Perlimy A2, Paldimycin; Paldimycin B, Paldimycin; Paldimycin B2, cin, Perlolyrine, Persipeptide A, Persipeptide B., PF 6766, Pamamycin, Pamamycin; Pamamycin 593, Pamamycin; Phaeochromycin A, Phaeochromycin B. Phaeochromycin C, Pamamycin 607, Pamamycin; Pamamycin 607, N-De-Me, Phaeochromycin D. Phaeochromycin E, Phaeochromycin F, Pamamycin; Pamamycin 663, Pamamycin; Pamamycin 677, Phaeochromycin G. Phaeochromycin H, Phagomycin, Phala Pamamycin; Pamamycin 691, Pamamycin; Pamamycin 705, mycin, Phebestin, Pheganomycin, Pheganomycin D. Phega Pamamycin; Pamamycin 621A, Pamamycin; Pamamycin nomycin D; 1'1-Deoxy, Pheganomycin DGPT. Pheganomy 621A, Homologue, Pamamycin; Pamamycin 635A, Pama cin DR, Phenalinolactone A, Phenalinolactone A: 1-Deoxy, mycin; Pamamycin 635A, Homologue, Pamamycin; Pama Phenalinolactone A; 6'-Methoxy, Phenalinolactone B. Phe mycin 649A, Pamamycin; Pamamycin 593B, Pamamycin; namide: (S)-form, Phenatic acid A. Phenatic acid B, 1-Phena Pamamycin 621B, Pamamycin; Pamamycin 635B, Pamamy Zinecarboxylic acid, 1-Phenazinecarboxylic acid; 5,10-Dihy cin; Pamamycin 649B, Pamamycin; Pamamycin 621C, dro, carboxymethyl ester, 1-Phenazinecarboxylic acid; Me Pamamycin; Pamamycin 635C, Pamamycin; Pamamycin ester, 1.6-Phenazinedicarboxylic acid, 1,6-Phenazinedicar 621D, Pamamycin; Pamamycin 635D, Pamamycin; Pama boxylic acid; 5,10-Dihydro, di-Meester, 1.6-Phenazinedicar mycin 635E, Pamamycin; Pamamycin 635F, Panclicins, Pan boxylic acid; Mono-Me ester, 1.6-Phenazinedicarboxylic glimycin D. Panglimycin D: 4-Deoxy, Pantomycin, Parimy acid; Mono-O-L-rhamnopyranosyl ester, 1.6-Phenazinediol. cin, Paromamine, Paromamine; 3'-Deoxy, Paromomycin, 1,6-Phenazinediol; Di-Meether, 1,6-Phenazinediol; 5,10-Di Paromomycin; 1-N Ac, Paromomycin; 6"-Deamino, 6"- oxide, 1,6-Phenazinediol; Mono-Me ether, 1,6-Phena hydroxy, Paromomycin; 3'-Deoxy, Paromomycin; 6-Deoxy, Zinediol, 5-Oxide, 1,2,6-Phenazinetriol: Tri-Me ether, Paromomycin; 5"-Epimer, Paromomycin; 5"-Epimer, 6"- 1-Phenazinol, 1-Phenazinol; Meether, 1-Phenazinol; (Meth deamino, 6"-hydroxy, Paromomycin; 5"-Epimer, 6-deoxy, oxycarbonylmethyl) ether, Phenazinoline A, Phenazinoline Partricin A, Partricin A; N-De-Me, Me ester, Partricin A, A: 11-Deoxy, Phenazinoline C, Phenazinoline D. Phenazino N-De-Me, Partricin A, 7-Deoxy, 5-alcohol, Partricin A; line D; 6,11-Dideoxy, 9, 14-dihydroxy, Phenazinomycin, 7-Deoxy, 5-alcohol, N-de-Me, Partricin A; Meester, Partricin Phenazostatin A, Phenazostatin B, Phenazostatin C, Phenel C, Parvulomycin, Paulomycin A, Paulomycin A; 6'-O-De famycin, Phenelfamycin; Phenelfamycin C, 23-DeCpheny Ac, 6'-propanoyl, Paulomycin A; 4'-O-Deacyl, Paulomycin lacetoxy), Phenelfamycin; Phenelfamycin C, 21-Epimer, A:3"-O-De-Me, Paulomycin A2, Paulomycin B, Paulomycin 23-de(phenylacetoxy), Phenel famycin; Phenelfamycin C, B: 4'-O-Deacyl, Paulomycin B; 3"-O-De-Me, Paulomycin C. O-De-(phenylacetyl), Phenelfamycin; Phenel famycin E, Paulomycin D. Paulomycin E. Paulomycin E: 3"-Epimer, Phenelfamycin; Phenelfamycin E, 23-DeCphenylacetoxy), Paulomycin F, Paulomycin F; 3"-Epimer, PD 125375, Pecti Phenelfamycin; Phenelfamycin E, 21-Epimer, 23-de(pheny natone; (Z)-Isomer, Peliomycin, Penicillin N. Penicillin N: lacetoxy), Phenelfamycin; Phenelfamycin E, O-De(pheny 3-De-C.-methyl, Penicillin N: 3-De-O-methyl, 5'-epimer, lacetyl), Phenelfamycin; Phenel famycin E, 31-Hydroxy, Penicillin N; 5'-Epimer, Penicillin N; 5'-Epimer, 5'-N-Ac, Phenelfamycin; Phenelfamycin F. Phenelfamycin; Phenelfa 5-Pentadecyl-1,3-benzenediol, 5-Pentadecyl-1,3-benzene mycin F, 31-Hydroxy, Phenocyclinone, Phenomycin, Pheny diol; Di-O-sulfate, 5-Pentadecyl-1,3-benzenediol; Mono-O- lacetic acid, Phenylacetic acid; Amide, Phenylacetic acid; sulfate, Pentaene G8, Pentaene I, Pentafungin, 2.3'44'.5- (6-Deoxy-O-L-talopyranosyl) ester, Phenylacetic acid; C-L- Pentahydroxy-7.9":7",9-diepoxylignan; (7S,7S,8R, 8R)- Rhamnopyranosyl ester, N-(Phenylacetyl)-2-butenediamide: form, 4.5-Methylene, 3'-Meether, 1,3,5,7,10-Pentahydroxy (E)-form, Phenylalanylisoleucylargininal; NPhe-(3-Meth 1,9-dimethyl-2H-benzoca pyrene-2,6(1H)-dione, 2',3',4'.5, ylbutanoyl), 4-Phenyl-3-butenoic acid; (E)-form, 2-Phenyl 7-Pentahydroxyisoflavone; 3'-Me ether, 3',4',5,6,7- ethylamine, 2-Phenylethylamine; N Ac, 2-Phenylethy Pentahydroxyisoflavone; 4,6-Di-Me ether, 3',4',5,7,8- lamine; N-(13-Methyltetradecanoyl), N-(2-Phenylethyl) Pentahydroxyisoflavone, 3',4',5,7,8- carbamic acid; Butyl ester, N-Phenyl-1-naphthylamine, Pentahydroxyisoflavone; 4.8-Di-Me ether, 3',4',6,7,8- N-Phenyl-2-naphthylamine, 4-Phenyl-3-(2-pyridinyl)-2- Pentahydroxyisoflavone; 4,6,7-Tri-Me ether, 2,3,5,7,10 buten-1-ol; (E)-form, Phepropeptin A, Phepropeptin A: 3-L- Pentahydroxy-9-methyl-6H-benzoca pyren-6-one, 1.3.10, Isoleucine analogue, Phepropeptin A; 1-L-Phenylalanine 11,12-Pentahydroxy-2-naphthacenecarboxamide, analogue, Phepropeptin A; 1-L-Phenylalanine, 3-L-isoleu US 2016/01 86168 A1 Jun. 30, 2016 76 cine analogue, Phosmidosine, Phosmidosine; O-De-Me, 15, 16-Dihydro, 15R-hydroxy, Platencin; 12S-Hydroxy, Pla 1"-N-Me, Phosmidosine; O-De-Me, Phosmidosine; tencin; 13R-Hydroxy, Platencin; 14S-Hydroxy, Platencin: N-Deprolyl, Phosmidosine; 1"-N-Me, Phosphazomycin A, 13R-Hydroxy, Me ester, Platencin; Methylthio ester ana N-(Phosphinothricylalanylalanyl)phosphinothrcin, Phosphi logue, 13R-hydroxy, 5'-O-B-D-glucopyranoside, Platencin nothricylalanyl-2-aminobutanoic acid, Phosphinothricylala A4, Platencin A4; 13R-Hydroxy, Platencin A4; 14S-Hy nylglycine, Phosphinothricylalanylserine, Phosphinothricy droxy, Platencin A7, Platencin A8, Platencinic acid; 2,3-Di lalanylvaline, Phosphinothricylglycylalanine, Streptomyces hydroxypropyl ester, Platencinic acid; 12R-Hydroxy, Platen Phospholipase C inhibitor, Phospholipase D, N5-Phospho cinic acid; 13R-Hydroxy, Platenocidin, Platenomycin A2, methionine sulfoximine; (S,S)-form, N-Phosphomethionine Platenomycin A2; 4B O-Deacyl, 4B-propanoyl, Plateno S-Sulfoximinylalanylalanine, Phosphophenylalanylarginine; mycin W3, Platensimide A, Platensimide A: 14B-Hydroxy, L-L-form, Phostriecin, Phycomycin, Phyllomycin, Physos 1-parent acid, Platensimide A, 14B-Hydroxy, 1-parent acid, tigmine, Physostigmine; N8-De-Me, Physostigmine; N1-De Me ester, Platensimide A: 1-Parent acid, Platensimide A: Me, N1-Ac, Physostigmine; N1,N8-Di-de-Me, N1-Ac, Phy 1-Parent acid, Me ester, Platensimycin, Platensimycin; toactin, Phytophthoradiene, Phytostreptin, PI 201, PI 201: Amide, Platensimycin; Decarboxy, Platensimycin; 6,7-Dihy Lactone, PI 220, Piceamycin, Piceamycin; 2,3-Dihydro, dro, 7 B-hydroxy, Platensimycin; 5'-O-B-D-Glucopyranoside, N-acetylcysteine adduct (R= SCH2CH(NHAc)COOH), Platensimycin; 12-Hydroxy, Platensimycin; 13 B-Hydroxy, Picromycin, Picromycin; 12-Deoxy, Picromycin; 12-Deoxy, Platensimycin; 14B-Hydroxy, Platensimycin; 17-Hydroxy, aglycone, Picromycin; 12-Deoxy, 14R-hydroxy, Picromycin; Platensimycin; 14.f3-Hydroxy, Meester, Platensimycin; Me 10, 11-Dihydro, Picromycin; 14R-Hydroxy, Piericidin; Anti ester, 5'-O-B-D-glucopyranoside, Platensimycin A5, Platen biotic IT 143A, Piericidin; Antibiotic IT 143A, 11 S*,12S*- simycin B2, Pleomycin, Plicacetin, Plicacetin: N-De-Me, Epoxide, Piericidin; Antibiotic IT 143B, Piericidin; Antibi Plicacetin: 3'B-Hydroxy, Plicacetin: 3'B-Hydroxy, 4"-N-Me, otic IT 143B, 5-Demethoxy, Piericidin; Antibiotic IT 143B, Plumbemycin A, Plumbemycin A; 3'-Amide, Pluracidomy 11S*,12S*-Epoxide, Piericidin; Piericidin A1, Piericidin; cin A1, Pluracidomycin A2, Pluracidomycin B, Pluracidomy Piericidin A1, 11", 12'-Epoxide, Piericidin; Piericidin A1, 10'- cin C2, Pluracidomycin C3, Pluracidomycin D. Plurallin, Me ether, 11", 12-epoxide, Piericidin; Piericidin A1, 4-O-D- Pluramycin B, PM 050463, PM 050463; 10'-O-B-D-Glu Glucopyranoside, Piericidin; Piericidin A1, 10'-O-B-D-Glu copyranoside, PM 060054, PM 060054; 10'-O-B-D-Glu copyranoside, Piericidin; Piericidin A1, 13'-Hydroxy. 10'-O- copyranoside, Polyketoacidomycin, Polyketomycin, Polyke B-D-glucopyranoside, Piericidin; Piericidin A1, 4-O-L- tomycin; 4B-Debenzoyl, Polyketomycin; 3"-Demethyl, Rhamnopyranoside, Piericidin; Piericidin A1, 4-O-(6- Polyketomycin; 6-Demethyl, Polyketomycin IP3, e-Polyl Deoxy-B-D-talopyranoside), Piericidin; Piericidin A1, ysine, Polyoxin A, Polyoxin A; 5-Carboxylic acid, Polyoxin 5-Demethoxy, Piericidin; Piericidin A1, O5-De-Me, Pierici A: 5-Dechydroxymethyl), Polyoxin A; 5-Deoxy, Polyoxin B, din; Piericidin A1, 5-Demethoxy, 10'-O-B-D-glucopyrano Polyoxin B: 5-Carboxylic acid, Polyoxin B: 5-Dechydroxym side, Piericidin; Piericidin A2, Piericidin; Piericidin A2, 11", ethyl) Polyoxin B: 5-Dechydroxymethyl), 5-fluoro, Polyoxin 12'-Epoxide, Piericidin; Piericidin A2, 10'-Meether, 11", 12'- B: 5-Dechydroxymethyl), 5-fluoro, 3'-deoxy, Polyoxin B; epoxide, Piericidin; Piericidin A3, Piericidin; Piericidin A3, 5-Dechydroxymethyl), 5-methyl, Polyoxin B; 3"-Deoxy, 11", 12'-Epoxide, Piericidin; Piericidin A3, 10'-Meether, 11", Polyoxin B; 3"-Deoxy, 5-carboxylic acid, Polyoxin C, Poly 12-epoxide, Piericidin; Piericidin A3,5-Demethoxy, Pierici oxin I, Polyoxin N. Polyoxin O, Polyoxypeptin A, Polyox din; Piericidin A4, Piericidin; Piericidin A4, 11", 12'-Epoxide, ypeptin A; 4"-Deoxy, Polyribonucleotide nucleotidyltrans Piericidin; Piericidin A4, 10'-Me ether, 11", 12'-epoxide, ferase, Porothramycin A, Porothramycin A; Me ether, Piericidin; Piericidin A5, 10-Me ether, N-oxide, Piericidin; Poststatin, Practomycin C, Prasinomycin, Prasinon A, Prasi Piericidin A5, 11'R*,12"R*-Epoxide, Piericidinol A1; non B. Prechrysophanol; (R)-form, 8-O-B-D-Glucuronopy 3-Epimer, 10-O-B-D-glucopyranoside, Piericidinol A1; ranoside, Prefluostatin, Prejadomycin-2-carboxylic acid, 10-O-B-D-Glucopyranoside, Pillaromycin A, Pillaromycin Prekinamycin, Prelasalocid, Prelasalocid; 18f3, 193:22B,23 B B1, Pillaromycin B2, Pillaromycin C, Pillarose; L-form, Pilo Diepoxide, Premithramycin B. Premithramycin B; 3A-O- quinone, Piloquinone: 4-Hydroxy, Pilosamycin, 9(11), 15-Pi Deglycosyl, Premithramycin B; 3C,8-Di-O-deglycosyl, maradien-3-ol; (ent-3f.8C)-form, O-Carbamoyl, 9(11), 15 Premithramycin B; 3D,8-Di-O-deglycosyl, Premithramycin Pimaradien-3-ol; (ent-3?,8C.)-form, O-(2-Amino-2- B; 3D,8-Di-O-deglycosyl, 4C-ketone, Premithramycin B; oxoacetyl), 9(11), 15-Pimaradien-3-ol; (ent-3f.8C)-form, 8-O-Deglycosyl, Premithramycin B; 9-Demethyl, 3C,8-di O-(2-Hydroxyamino-2-oxoacetyl), 9(11), 15-Pimaradien-3- O-deglycosyl, Premithramycin B; 9-Demethyl, 3D,8-di-O- ol; (ent-3f.8C.)-form, O-2-(Acetylhydroxyamino)-2- deglycosyl, Premithramycin B; 9-Demethyl, 3D,8-di-O-deg oxoacetyl, 9(11), 15-Pimaradien-3-ol; (ent-3f.8C)-form, lycosyl, 4C-ketone, Premithramycin B; 9-Demethyl, 8-O- O—N-(2-Hydroxyethyl)aminocarbonylcarbamoyl, deglycosyl, Premithramycinone, Premithramycinone; O-De 9(11), 15-Pimaradien-3-ol; (ent-3f.8C.)-form, 3-Ketone, Me, Premithramycinone G. Premithramycinone H, Pimaricin, Pimaricin; Amide, Pimaricin; Deepoxy, 4.5-dide Prenomycin, 3-Prenyltyrosine: (S)-form, 3-Prenyltyrosine: hydro, Pinoresinol; (+)-form, Pinoresinol; (+)-form, (S)-form, N. Ac, Primycin, Pristinamycin IC, Pristinamycin 7-Epimer, Piperastatin A, Piperastatin B, Piperazimycin A, IC: N4'-De-Me, Probestin, Proceomycin, Procidin S 346, Piperazimycin A; 8-Deoxy, Piperazimycin C, Pironetin, Procidin S 735, Proclavaminate amidinohydrolase, Procla Pironetin: O-De-Me, Pitucamycin, Placetin, Pladienolide A, Vaminic acid, Prodigiosin, Prodigiosin R1, Promoinducin, Pladienolide A: 7-Ac, Pladienolide A: 6-Deoxy, 7-Ac, Pladi Promothiocin A, Promothiocin B. Prostatin, Protactin, Strep enolide A: 165-Hydroxy, Pladienolide A: 205-Hydroxy, Pla tomyces chromofuscus Protease inhibitor, Streptomyces liv dienolide A: 165-Hydroxy, 7-Ac, Pladienolide A: 205-Hy idans Protease inhibitor, Protein AN 1, Protetrone, Prothra droxy, 7-Ac, Pladienolide A: 17-Hydroxy, 21-Meether, 7-Ac, carcin: (S)-form, Protocidin, Protostreptovaricin I, Pladienolide A: 21-Ketone, 7-Ac, Plasminostreptin, Platen Protostreptovaricin I; O10-De-Me, Protostreptovaricin I; cin, Platencin; 15, 16-Dihydro, 15R, 16-dihydroxy, Platencin: 14C.-Hydroxy, Protostreptovaricin I; 14C-Hydroxy, 19-Me

US 2016/01 86168 A1 Jun. 30, 2016 79 acid, Me ester, Siomycin A; T-Parent amide, Siomycin A; tophenazine B, Streptophenazine D. Streptophenazine E. 1.2R,49S.49'-Tetrahydro, 26-thione, 1'-parent acid, Siomy Streptophenazine F. Streptophenazine G. Streptopyrrole, cin A 1,2R,49S.4'-Tetrahydro, 26-thione, 1'-parent acid, Me Streptopyrrole; Bromo analogue, Streptopyrrole: 1-Chloro, ester, Siomycin A; 1.2R,49S.49'-Tetrahydro, 26-thione, Streptopyrrole: 1-Chloro, 6-Meether, Streptopyrrole: 6-Me 4'-parent amide, Siomycin A; 1.2R,49S.49'-Tetrahydro, ether, Streptorubin B, Streptothricin; Streptothricin A, Strep 26-thione, 7-parent amide, Siomycin D1, Sisomicin, Sisto tothricin; Streptothricin B, Streptothricin; Streptothricin B, mycosin, Skylamycin A, SNA 4606-1, SNF 4435C, SNF 4'-O-Decarbamoyl, 6'-O-carbamoyl, Streptothricin; Strepto 4435C. 6-Epimer, Solumycin, Soulomycin, Sparsomycin, thricin C, Streptothricin; Streptothricin C, NB-Ac, Strepto Sparsomycin; S15-Oxide (R-), Sparsomycin; S15-Oxide thricin; Streptothricin C, 4'-O-Decarbamoyl, 6'-O-carbam (S-), SP-Chymostatin B, SP-Chymostatin B; 1-Alcohol, SP oyl, Streptothricin; Streptothricin D. Streptothricin; Chymostatin B: 2-Epimer, SP-Chymostatin B; 2-Epimer, Streptothricin D, NB-Ac, Streptothricin; Streptothricin D, 4'-hydroxy, SP-Chymostatin B; 4"-Hydroxy, Spectinabilin, N5-Me, Streptothricin; Streptothricin D. 4'-O-Decarbamoyl, Spectinabilin; 2',3'-Didehydro, Spectinomycin, Spectinomy 6'-O-carbamoyl, Streptothricin; Streptothricin E. Streptothri cin: 4R-Alcohol, Spectomycin A2, Spectomycin A2; 8-Me cin; Streptothricin E, NB-Ac, Streptothricin; Streptothricin E, ether, Spectomycin B1, Spenolimycin, Sphinin, Sphydrofu 6'-O-Carbamoyl, NB-Ac, Streptothricin; Streptothricin E, ran, Spinamycin, Spiramycin S, Spiramycin S. 18-Aldehyde, 4'-O-Decarbamoyl, 6'-O-carbamoyl, Streptothricin; Strepto Spiramycin S; 18-Aldehyde, 3-propanoyl, Spirodionic acid, thricin F. Streptothricin; Streptothricin F, NB-Ac, Streptothri Spirofungin A, Spirofungin A; 15-Epimer, Spirohexenolide cin; Streptothricin F 4'-O-Decarbamoyl, 6'-O-carbamoyl, A, Spirohexenolide A: 8-Deoxy, Spironaphthodione, Spleno Streptothricin; Streptothricin F 4'-Decarbamoyl, 6-carbam cin, Stambomycin, Staurosporine, Staurosporine; 4'-N-(Ac oyl, NB-Ac, Streptothricin; Streptothricin F 1'-Epimer, 4'-de etoxymethoxy), Staurosporine; 4'-N-Carbamoyl, Staurospo carbamoyl, 6'-carbamoyl, NB-Ac, Streptothricin; Streptothri rine; O-De-Me, Staurosporine; 4'o.5'C-Dihydroxy. 4'-de cin F, 3a-Epimer, 4'-decarbamoyl, 6'-carbamoyl, NB-Ac, (methylamino), Staurosporine; 7-Epimer, 7-hydroxy, Streptothricin; Streptothricin X, Streptothricin acids, Strep Staurosporine; 3'-Epimer, 4'-hydroxy, 4-de(methylamino), tothricin acids; Streptothricin C acid, NB-Ac, Streptothricin Staurosporine; 4'-N-Formyl, Staurosporine: 75-Hydroxy, acids; Streptothricin D acid, NB-Ac, Streptothricin acids: Staurosporine; 4'-N-Hydroxy, 4-N-de-Me, 4-N-formyl, Streptothricin Dacid, 4'-Decarbamoyl, 6'-carbamoyl, Strep Staurosporine; 4'-Hydroxy, 4-de(methylamino), Staurospo tothricin acids; Streptothricin Dacid, NB-Me, NB-Ac, Strep rine, 4-N-Me, Staurosporine; 4'C.-Nitro. 4'-de(methy tothricin acids; Streptothricin E acid, NB-Ac, Streptothricin lamino), Staurosporine: 7-Oxo, Staurosporinone, Stauro acids: Streptothricin E acid, 6'-Carbamoyl, NB-Ac, Strepto sporinone; N13-(2,6-Dideoxy-C-D-ribo-hexopyranosyl), thricin acids; Streptothricin E acid, 4-Decarbamoyl, 6'-car Staurosporinone; N6-(1-Methylethoxy)methyl, Stawamy bamoyl, Streptothricin acids; Streptothricin Facid, 4'-Decar cin, Stealthin A, Stealthin A; 12-Aldehyde, Stealthin C, Stef bamoyl, 6-carbamoyl, Streptothricin acids; Streptothricin F fimycin, Steffimycin; Aglycone, 105-alcohol, Steffimycin; acid, 4'-Decarbamoyl, 6'-carbamoyl, NB-Ac, Streptovaricin 4A-Me ether, Steffimycin; De?glycosyloxy), 2-demethoxy, C. Streptovaricin C: 17-Ac, Streptovaricin C; 21-Ac, Strep Steffimycin; 2-Demethoxy, Steffimycin; 8-Demethoxy, Stef tovaricin C; 24-Deoxy, Streptovaricin C; 16-Hydroxy, Strep fimycin; 2-Demethoxy, 4A-O-3-(2,5-dihydro-4-methyl-2,5- tovaricin C; 16 B-Hydroxy, 17-Ac, Streptovaricin C; 16.f3-Hy dioxo-3-furanyl)propanoyl), Steffimycin; 2-Demethoxy, droxy, 21-Ac, Streptovaricin C: 17-Ketone, Streptovaricin F, 5-imine, Steffimycin; 10-Deoxo, Steffimycin; 10-Deoxo, Streptovaricin U. Streptoverticillin, Streptovitacin D. Strep 4A-Me ether, Steffimycin; 10-Deoxo, O2-de-Me, Steffimy tozotocin, Strepturidin, Stresgenin B, Streptomyces Subtili cin; 10-Deoxo, 8-demethoxy, Steffimycin; 10-Deoxo, sin inhibitor-like proteins, Streptomyces Subtilisin inhibitor, 8-demethoxy. 2A-O-de-Me, Steffimycin; 10-Deoxo, 2,8-di Succinimycin, Suidatrestin, Suinin, Suitamycin, Sulfinemy demethoxy. 2A-O-de-Me, Stendomycin, Stenothricin, Stra cin, Sulfomycin, Sulfomycin; Sulfomycin I, Sulfomycin; vidin S2, Stravidin S3, Strepin P1, Streptavidin, Streptazo Sulfomycin I, N49-Parent amide, Sulfomycin; Sulfomycin I, line, Streptazoline; 13-Hydroxy, Streptazoline; 9R-Hydroxy, N52-Parent amide, Sulfomycin; Sulfomycin I, Streptazoline; 5-O-B-D-Xylopyranoside, Streptazone B1, 21-Demethoxy, Sulfomycin; Sulfomycin I, 5-Methyl, Sulfo Streptazone B1; 45.4a3-Epoxide, Streptazone B1; (E)-Iso mycin; Sulfomycin III, 65-Deoxy, 21-O-de-Me, Sulfomycin; mer, Streptazone C, Streptimidone, Streptin, Streptin P1, Sulfomycin III, 65-Deoxy, 21-demethoxy, Sulfur, Sulfur Streptocidin A, Streptocidin A; 3-D-Tryptophan analogue, (S8), Sulfurmycin B, Sulfurmycin B: 1-Hydroxy, Sulfurmy Streptocidin A; 3-L-Tryptophan analogue, Streptocidin A; cin B; 11-Hydroxy, Sulfurmycin C, Sulfurmycin C: 3-L-Tryptophan, 10-D-phenylalanine analogue, Streptofac 3B-Deoxy, Sulfurmycin D. Sulfurmycin D; 9-Epimer, 1-hy tin, Streptogan, Streptogrisin A, Streptogrisin B, Strepto droxy, Sulfurmycin D; 11-Hydroxy, N-di-de-Me, Sulfurmy hexin, Streptoketol B, Streptolydigin, Streptomutin A, Strep cin F. Sulfurmycin F. Aglycone, Sulfurmycin F; Aglycone, tomyceamide A, Streptomyceamide B, Streptomycin, 7-deoxy, Sulfurmycin F: Aglycone, 11-hydroxy, Sulfurmycin Streptomycin; N-De-Me, Streptomycin; 2-Deoxy, Strepto F; 3B-Deoxy, Sulfurmycin F; 4C-Epimer, Sulfurmycin F; mycin; 5'-Hydroxy, Streptomycin; 5'-Hydroxy. 4"-O-B-D- 4C-Ketone, Sulfurmycin F; 7-De?glycosyloxy), 1-hydroxy, mannopyranosyl, Streptomycin; 4"-O-O-D-Mannopyrano Sulfurmycin F; 11-Hydroxy. 4C-ketone, Sulfurmycin F; syl-(1->6)-O-D-mannopyranosyl, Streptomycin; 4'-O-B-D- 1-Hydroxy, 4C-ketone, Sulphostin, Swalpamycin, Swalpa Mannopyranosyl, Streptomycin 3"-kinase, Streptomycin mycin; 10, 11-Dihydro, 12S,13S-epoxide, Swalpamycin; 6-kinase, Streptomycin-Park nucleotide antibiotic, Strepto 12S,13S-Epoxide, Swalpamycin; 8(3-Hydroxy, 12S,13S-ep mycin-6-phosphatase, Streptonigrin, Streptonigrin, 10'-O- oxide, Syriamycin, T 76, TA 2590, Taitomycin, Taitomycin; De-Me, Streptonigrin: 6-O-De-Me, Streptonigrin: 10'- Taitomycin B. Takamycin, Takanawaenes; Takanawaene A, Demethoxy, Streptonigrin F. Streptonigrin P1, Streptonigrin Takanawaenes; Takanawaene B, Takanawaenes; P2, Streptonigrone, Streptophenazine A, Streptophenazine A. Takanawaene C, Talopeptin, Talopeptin; 4A-Epimer, Tamb 6'-Hydroxy, Streptophenazine A; 6-Parent acid, Strep jamine A. 1"-N-Dodecyl, TAN 1307, TAN 1030A, TAN

US 2016/01 86168 A1 Jun. 30, 2016 bacteriohopanetetrol; (2B,32R,33R.34S)-form, 35-O-O-D- anoyl, Micropeptin 478A, Micropeptin 478A; Dechloro, Glucuronopyranoside, 2-Methyl-32,33,34,35 4'-deoxy, Micropeptin 478A; Dechloro. 4'-deoxy, O-des bacteriohopanetetrol; (2B,325.335.345)-form, 35-O-O-D- ulfo, Micropeptin 478A; Dechloro. 4'-deoxy, O-desulfo, Altruronopyranoside, 2-Methyl-32,33,34,35 2'-O-sulfate, Micropeptin 478A; Dechloro, 4"-deoxy, 6"-Me bacteriohopanetetrol; (23.325.335.345)-form, 35-O-(3,6- ether, Micropeptin 478A: Dechloro, 4'-deoxy, 6"-Meether, Anhydro-B-D-galacturonopyranoside), 2-Methyl-2,6- N-deacyl, Micropeptin 478A: Dechloro, 4"-deoxy, 6"-Me eicosadienoic acid; (2E,6E)-form, (2-Hydroxyethyl)amide, ether, O-desulfo, Micropeptin 478A; Dechloro. 4'-deoxy, 2-Methyl-2,6-eicosadienoic acid; (2E,6E)-form, (2-Ac 6"-Me ether, O-desulfo. 2'-O-sulfate, Micropeptin 478A: etoxyethyl)amide, 2-Methylheptadecane, 6-Methylheptade Dechloro. 4'-deoxy, 6"-Meether, 2'-O-sulfate, Micropeptin cane, 7-Methylheptadecane, 7-Methyl-1H-indole-3-carbox 478A; Dechloro. 4'-deoxy. 2'-O-sulfate, Micropeptin 478A: aldehyde; N-Me, 2-Methyl-29-(1,2,3,4,5- Dechloro. 2'-O-sulfate, Micropeptin 478A: O-Desulfo, pentahydroxypentyl)hopane; (23.225.31S,32R-33S.34R)- Micropeptin 478A: Lower homologue (R= -CH(CH3)2), form, 2-Methyl-29-(2,3,4,5-tetrahydroxypentyl)-29 4", 6"-di-Me ether, O-desulfo, Micropeptin 478A: Lower hopanol; (2|B,225.29R.32R,33R,34R)-form, Microcin SF homologue (R= -CH(CH3)2), 4"-Me ether, Micropeptin 608, Microcin SF 608; 2.2'2",3a,7a-Pentaepimer, Microcin 478A: Lower homologue (R= -CH(CH3)2), 4"-Me ether, SF 608: 2,2'2",3a,7a-Pentaepimer, 2"-Ac, Microcin SF 608: O-desulfo, Micropeptin 478A: Lower homologue (R= -CH 2.2.3a,7a-Tetraepimer, Microcolin A, Microcolin A; Deoxy, (CH3)2), 2'-O-sulfate, Micropeptin 478A: 4"-Me ether, Microcolin A; Deoxy, O-de-Ac, Microcydamide A, Microcy Micropeptin 478A: 4"-Me ether, 2'-O-sulfate, Micropeptin damide A: 21-Epimer, Microcydamide 7806A, Microcyda 478A: 2'-O-Sulfate, Micropeptin 88A, Micropeptin 88B, mide 7806B, Microcydamide GL616, Microcyclamide Micropeptin C, Micropeptin 88C, Micropeptin 88C; 5"-Me GL628, Microcyclamide GL628; O-De-Me, Microcydamide ester, Micropeptin D. Micropeptin 88D, Micropeptin GL546A, Microcyclamide GL546A: 21-Epimer, Microcyda DR1006, Micropeptin DR1060, Micropeptin DR1060:4".5", mide GL614A, Microcydamide GL614A; 21-Epimer, Micro 6",7"-Tetradehydro, Micropeptin E, Micropeptin 88E, cystin, Microcystin; Microcystin EE, N7-De-Me, 4-Me ester, Micropeptin EI 992, Micropeptin EI 992: N-Debutanoyl, Microcystin; Microcystin EE, N7-De-Me, 2,4-di-Me ester, N—Ac, Micropeptin F. Micropeptin GH979, Micropeptin Microcystin; Microcystin EE, 3-D-Aspartic acid analogue, GH979:4"-Amide, Micropeptin HA983, Micropeptin K 139, N7-de-Me, 4-Me ester, Microcystin; Microcystin EE, 3-D- Micropeptin MM836, Micropeptin MM836: 28-Hydroxy, Aspartic acid analogue, N7-de-Me, 2,4-di-Meester, Micro 48-sulfo, Micropeptin MM836: 39-Me ether, Micropeptin cystin; Microcystin EE, 7-L-Serine analogue, N7-de-Me, MM836: 48-Sulfo, Micropeptin MM978, Micropeptin 88N, 4-Me ester, Microcystin; Microcystin EE, 7-L-Serine ana Micropeptin SD1002, Micropeptin SD944, Micropeptin logue, NT-de-Me, 2,4-di-Meester, Microcystin; Microcystin SD979, Micropeptin SD999, Micropeptin SF909, Micropep EE, 3-D-Aspartic acid analogue, 7-L-serine analogue, tin SF995, Micropeptin T1, Micropeptin T2, Micropeptin N7-de-Me, 2,4-di-Me ester, Microcystin; Microcystin LR, T20, Micropeptin 88Y, Microphycin AL828, Microviridin A, 1-D-Leucine analogue, Microcystin; Microcystin LR, 3-D- Microviridin B, Microviridin C, Microviridin D, Microviri Aspartic acid analogue, Microcystin; Microcystin LR, 3-D- din E, Microviridin F, Microviridin H, Microviridin H: (1"- Aspartic acid analogue, N7-de-Me, Microcystin; Microcystin >3")-Lactone, O-de-Me, Microviridin I, Microviridin LR, O-De-Me, Microcystin; Microcystin LR, N7-De-Me, SD1684, Microviridin SD1684; Parent acid, Glu-5->Ser Microcystin; Microcystin LR, 7-L-Serine analogue, N7-de Asp->Thrdilactone, Microviridin SD1684; Parent acid, Me, Microcystin; Microcystin LR, 7-L-Serine analogue, Glu-5->Serlactone, Microvirin, Microvirin, Minutissamide Microcystin; Microcystin LR, 2-L-Homoisoleucine ana A, Minutissamide A, 12'-Chloro, Minutissamide C, Minutis logue, Microcystin, Microcystin LR, 7-L-Lanthionine ana samide C; 145-Alcohol, Mirabazole A, 4',5'-Didehydro, logue. Microcystin; Microcystin LR, 4-L-Phenylalanine ana Mirabazole B, Mirabazole C, Mirabimide E, Mirabimides: logue, Microcystin; Microcystin LR, 4-L-Tryptophan Mirabimide A, Mirabimides; Mirabimide B, Mirabimides; analogue, Microcystin; Microcystin RR, Microcystin; Micro Mirabimide C. Mirabimides; Mirabimide D, Molassamide, cystin RR, N7-De-Me, Microcystin; Microcystin RR, 3-D- Mozamide A: Deoxy, Mozamide B: Deoxy, Mueggelone, Aspartic acid analogue, Microcystin; Microcystin RR, 3-D- Muscoride A, Mytilin A, Myxol; 2'-O-6-Deoxy-C-L-gluco Aspartic acid analogue, N7-de-Me, Microcystin; Microcystin side, Myxol; 2'-O-(2,4-Di-O-methyl-O-L-fucopyranoside), RR, 7-L-Serine analogue, Microcystin; Microcystin RR, Myxol; 2'-O-O-L-Fucopyranoside, Myxol; 2'-O-(3-O-Me 3-D-Aspartic acid, 7-(N-methyl-L-serine) analogue, Micro thyl-O-L-fucoside), Myxol; 2'-O-O-L-Rhamnopyranoside, cystin; Microcystin RR, 3-D-Aspartic acid analogue, 6-Me Nakienone A, Nakienone B, Nakienone C, Nakitriol, Nha ester, Microcystin; Microcystin YR, Microcystin; Microcys trangin A, Nhatrangin A; 9-Bromo, Nodulapeptin B, Nodu tin YR, 2-(2-Amino-3-(4-hydroxy-2-cyclohexen-1-yl)pro lapeptin B; S-Oxide, Nodularin, Nodularin; 9-O-De-Me, panoic acid analogue, D-Asp3.(E)-Dhb7Microcystin Nodularin; 3'-Demethyl, Nodularin; Homoarginine ana HilR. (ADMAdda5)Microcystins, Microginin, Microginin logue, Nodularin; 6Z-Isomer, 1-Nonacosene-4,6,8,10,12,14. 478, Microginin 299A, Microginin 299A. 1-Chloro, Micro 16, 18.20.22.24-undecol; (4S,6S,8S, 10S, 12S, 14R,16R,18R, ginin 299A. 1-Chloro, detyrosyl, Microginin 299A: 20R.22R,24R)-form, Undeca-Me ether, 1-Nonadecene-4,6, Dechloro, Microginin 51A, Microginin 51A; N3-Me, Micro 8,10,12,14-hexol; (4S,6S,8S,10R,12R,14R)-form, Hexa-Me ginin 91A, Microginin 91A, 10-Chloro, Microginin 99A, ether, 20-Nor-5,7,9,11,13-abietapentaene-3,12-diol; Microginin 99A. 1-Chloro, Microginin AL584, Microginin 3C-form, 3-Ac, 20-Nor-5,7,9,11,13-abietapentaen-3-ol; 91C, Microginin 91C: 10-Chloro, Microginin 91C: 10,10 3C-form, Ac, Noscomin, Nostocine A, Nostoclide I, Nosto Dichloro, Microginin FR1, Microginin GH787, Microginin clide I: Mono-dechloro, Nostocyclamide, Nostocyclamide SD755, Microginin SD755; N3-De-Me, Microguanidine M, Nostocyclin, Nostocyclopeptide A1, Nostocyclopeptide AL772, Micromide, Micropeptin 103, Micropeptin 90, A2, Nostocyclopeptide M1, Nostocyclophane C, Nostocy Micropeptin A, Micropeptin A; N-Deoctanoyl, No)-hex clophane C: 1-Me ether, Nostocyclophane C: 1-Me ether,

US 2016/01 86168 A1 Jun. 30, 2016

didehydro, N—Ac, O-sulfate. Thienamycin; 6,8-Diepimer, 0114. In some embodiments, an organism can selected for 1'.2Z-didehydro, N. Ac, O-sulfate. Thiol sulfotransferase, an increase in any of the compounds described above. Thiopalmyrone. Thiosulfate-dithiol sulfurtransferase, Tigli 0115 Based on knowledge of the desired chemical prod camide A, Tiglicamide B, Tiglicamide C, Tjipanazole J, Toly uct (or compound), and the likely pathways involved (pri byssidin A, Tolybyssidin B, Tolypodiol, Tolypophycin, Toly mary and secondary), the following strategies can be porphin D, Tolyporphin D; 2A-Ac, Tolyporphin D; 2A2B employed for creating mutant libraries. Di-Ac, Tolyporphin D; 2B Ac, Tolyporphin D; 7,17 0116 First, several parameters may affect oligonucleotide Bisdeglycosyl, 7-acetoxy, 17-hydroxy, Tolyporphin D; 7,17 (oligo) incorporation. These parameters include chemical Bisdeglycosyl, 7,17-diacetoxy, Tolyporphin D; 7,17 modifications of oligonucleotides, the type of mismatch, and Bisdeglycosyl, 7-hydroxy, 17-acetoxy, Tolyporphin D; the number of bases between mismatches being introduced. 7-Deglycosyl, 7-acetoxy, 2B Ac, Tolyporphin D; 7-Degly General guidelines for optimizing allelic replacement cosyl, 7-hydroxy. 2B Ac, Tolyporphin J. Tolyporphin K. include: (1) avoiding the MMR system; (2) using an oligo 1.3.27.29-Triacontanetetrol; (3R,27S,29R)-form, 1-O-O-D- Suitable for lagging-Strand incorporation; (3) using Saturating Galactopyranoside, 1.3.27.29-Triacontanetetrol; (3R,27S, oligo concentrations; (4) using an appropriate size oligo as 29R)-form, 1-O-O-D-Glucopyranoside, 1.3.27.29-Triacon determined for the organism (approximately 70-90 bases, for tanetetrol; (3R,27S.29R)-form, 3-Ketone, 1-O-O-D- example in E. coli); (5) placing altered bases more than about galactopyranoside, 1.3.27.29-Triacontanetetrol; (3R,27S, 9 bases from an oligo end. 29R)-form, 3-Ketone, 1-O-O-D-glucopyranoside, 1.3.27.29 0117. In various embodiments, the oligonucleotide library Triacontanetetrol; (3R,27S,29R)-form, 27-Ketone, 1-O-O- includes one or more of the following features to induce D-glucopyranoside, 3,4,5-Tribenzyl-2(5H)-furanone; (+)- genetic diversity in the host cell. form, 2.3.5-Tribromo-4-hydroxybenzaldehyde, 2,3,5- 0118. The oligonucleotide library may target the selected Tribromo-4-hydroxybenzyl alcohol, Trichamide, 1,1,1- genes for varying promoter strength. In such embodiments, Trichloro-5-undecylamine; (+)-form, N. Ac, 1-Tricosene-4, the oligonucleotide library contains, for each of the targeted 6,8,10,12,14.20-heptol; (4S,6S,8S, 10R,12R,14R,20R)- genes, two, three, four, or five of the following promoters: T7. form, Hepta-Me ether, 1-Tricosene-4,6,8,10,12,14,16,18 Trc, T3, T5, and/or any of the known E. coli endogenous octol; (4S,6S,8S, 10S,12R,14R,16R,18R)-form, Octa-Me promoters. See, e.g., Harley and Reynolds, Analysis of E. coli ether, 6-Tridecylamine; (5)-form, N—Ac, 4,5,7-Trihydroxy promoter sequences, Nucleic Acids Res. Vol. 15, No. 5, 2343 isoflavone; 7-O-(6-Deoxy-C-L-talopyranoside), 4.5,7-Tri 2361 (1987). Further, these promoters can include oligo hydroxyisoflavone; 4,7-Di-O-(6-deoxy-C-L-talopyrano nucleotide degeneracy in the promoter region (e.g., from one side), 9,12,13-Trihydroxy-10, 15-octadecadienoic acid; (9S. to five degenerate positions) to provide a continuum of pro 10E, 12R,13S, 15Z)-form, 2.6.6-Trimethyl-1-cyclohexene-1- moter strengths for screening. carboxaldehyde, Trungapeptin A, Trungapeptin A; 7.8- 0119) Alternatively, or in addition, the oligonucleotide Dihydro, Trungapeptin A 7,7,8,8-Tetrahydro, Tryptamine: library may target the genes for varying translational effi Nb-(7S-Methoxy-4E-tetradecenoyl), Tubercidin, Tuberci ciency. In Such embodiments, the ribosomal binding site, or din; 5'-O-D-Glucopyranosyl, Tumonoic acid A, Tumonoic other sequence known to effect RNA turnover or translational acid A.; Etester, Tumonoic acid A. Meester, Tumonoic acid B, efficiency, is made degenerate to provide a continuum of Tumonoic acid B; Meester, Tumonoic acid C, Tumonoic acid translational strengths. For example, the Shine-Dalgarno D, Tumonoic acid E. Tumonoic acid F. Tumonoic acid G., sequence may be rendered degenerate at from one to five Tumonoic acid H. Tumonoic acid I, Tychonamide A, Tycho positions in Some embodiments. namide A, 13-Demethoxy, Tyropeptin A, Tyropeptin B, I0120 In some embodiments that employ eukaryotic cells Tyrostatin, Ulongamide B, Ulongamide B: 4"-Deoxy, Ulon (e.g., yeast), one or more sites relating to splicing efficiency gamide C. Ulongamide D, Ulongamide E. Ulongamide F. may be rendered degenerate at from one to five positions, to Ulongapeptin, Venturamide A, Venturamide B, Veraguamide provide a continuum in splice efficiency for the targeted A. Veraguamide A: Debromo, Veraguamide A: Debromo, genes. 35.35.36.36-tetrahydro, Veraguamide B, Veraguamide B: I0121. In some embodiments, the coding region of the Debromo, Veraguamide B: Debromo. 35.35.36.36-tetrahy genes is targeted for degeneracy, to provide a continuum of dro, Veraguamide D, Veraguamide E. Veraguamide F, Virida protein activity, so as to provide up and/or downregulation of mide A, Viridamide A: Lower homologue (R-CH3), Vitamin key enzymes at the functional level. In these embodiments, B12f, Welwitindolinone A isonitrile, Welwitindolinone B the oligonucleotides contain from 1 to 20, or from 1 to 10, or isothiocyanate, Welwitindolinone B isothiocyanate; 13, 14 from 1 to 5 degenerate positions, or combinations thereof at Didehydro, Welwitindolinone B isothiocyanate; 13, 14-Dide multiple locations in the oligo. hydro, N-Me, Welwitindolinone B isothiocyanate; 13, 14-Di I0122. In some embodiments, the oligonucleotide library dehydro, N-Me, isocyanide, Welwitindolinone B produces a premature stop codon in genes of potentially com isothiocyanate: 3-Hydroxy, 13.14-didehydro, N-Me, Welwit peting pathways, and/or screens seemingly unrelated meta indolinone B isothiocyanate: 3-Hydroxy, 13.14-didehydro, bolic genes for the effects of this inactivation on the desired N-Me, isocyanide, Welwitindolinone B isothiocyanate; phenotype (e.g., compound production). N-Me, Welwitindolinone D isonitrile; N-Me, Wewakazole, I0123. In some embodiments, a tag refers to a protein that is Wewakpeptin A. Wewakpeptin A; 7,7,8,8-Tetrahydro, fused to another protein to create a tagged protein. The tag Wewakpeptin C, Wewakpeptin C; 7,8-Tetrahydro, Yanucam sequence is often fused in-frame to the endogenous protein ide A, Yanucamide B, and Ypaoamide. coding sequence Such that a fusion protein is generated. In 0113. Additional compounds can be found in Blunt & frame means that the open reading frame (ORF) of the chro Munro, Dictionary of Marine Natural Products with CD mosomal sequence encoding the protein is maintained after ROM, Chapman and Hall/CRC (Sep. 19, 2007), the contents the insertion of the tag sequence. In-frame insertions occur of which are incorporated by referwence in its entirety. when the number of inserted nucleotides is divisible by three, US 2016/01 86168 A1 Jun. 30, 2016 90 which may be achieved by adding a linker of any number of I0129. The protein also may be tagged with more than one nucleotides to the tag protein encoding sequence as appli tag. For instance, a protein may be tagged with at least one, cable. A protein may be tagged anywhere within the protein two, three, four, five, six, seven, eight, or nine tags. More than polypeptide sequence provided the function of the protein is one tag may be expressed as a single polypeptide fused to a not affected. Generally, tagging is at the N- or C-terminus of protein of interest. More than one tag fused to a protein may the protein. be expressed as a single polypeptide which is cleaved into the 0124. A tag sequence may be any peptide sequence individual tag polypeptides after translation. encoded by a nucleic acid sequence. Tag sequence may 0.130. In some embodiments the tags may promote syn encode a variety of tags including, but not limited to, epitope thetic scaffolding. Scaffolding of proteins can increase the tags, affinity tags, reporters, or combinations thereof. local concentration of metabolites and alter the stoichiometry of the catalytic centers to balance flux through the metabolic 0.125. In some embodiments, the tag is an epitope tag. The pathway of interest. For instance SH3 domain(s) and their epitope tag may comprise a random amino acid sequence, or cognate peptides could be engineered with linkers to produce a known amino acid sequence. A known amino acid sequence various specific ratios between two or more desired proteins may have, for example, antibodies generated against it, or Such as enzymes. Methods which increase specific protein there may be no known antibodies generated against the protein interactions can be used and include the use of SH3 sequence. The epitope tag may be an antibody epitope tag for domains and peptides, leucine Zippers, PDZ domains and which commercial antibodies are available. Non-limiting peptides, GBD domains and peptides, PhyB/Pif3, FKBP/ examples of suitable antibody epitope tags include but are not FRB, or cohesin/dockerin limited to myc, AcV5, AU1, AU5, E, ECS, E2, FLAG, HA, I0131. In some embodiments, the tags may alter expres Maltose binding protein, nus, Softag 1, Softag 3, Strep, SBP. Sion, folding, or degradation of recombinant proteins in the Glu-Glu, HSV, KT3, S, 51, T7, V5, VSV-G, 6xHis, BCCP, target host organism. Protein stability may be altered by teth and calmodulin. ering to an affinity tag. Tags, such as maltose binding protein, 0126. In some embodiments, the tag is a reporter. Non by way of illustration, may alter the folding properties of the limiting examples of reporters include affinity tags, visual nascent desired protein(s) preventing degradation or removal reporters or selectable-marker reporters. Non-limiting to, for instance, bacterial inclusion bodies. examples of affinity tags include chitin binding protein (0132. In some embodiments, the invention can be used to (CBP), thioredoxin (TRX), poly(NANP), tandem affinity conduct protein or peptide engineering on proteins or pep purification (TAP) tag, and glutathione-S-transferase (GST). tides such as enzymes, antibodies, or proteins and peptide Visual reporters typically result in a visual signal. Such as a hormones important to human health Such as insulin. For color change in the cell, or fluorescence or luminescence of instance, combinatorial mutations could be introduced into the cell. For instance, the reporter Lacz, which encodes 3-ga an enzyme to provide a library of related proteins which could lactosidase, will turn a cell blue in the presence of a suitable be screened for improved physical or biochemical properties Substrate, such as X-gal. Other non-limiting examples of such as thermostability, feedback inhibition, substrate pref visual reporters include a fluorescent protein, luciferase, alka erence, pH optimum, k, or K. Similarly, desired mutations line phosphatase, beta-galactosidase, beta-lactamase, horse could be introduced based structural, sequence, or biochemi radish peroxidase, and variants thereof. Selectable-marker cal knowledge to introduce specific desired changes singly or reporters typically confer a selectable trait to the cell, such as combinatorially. drug resistance (e.g. antibiotic resistance). 0133. These libraries can be further constructed as 0127. In various embodiments, the tag is a fluorescent described herein or as synthetic allelic libraries, and protein visual reporter. Non limiting examples of fluorescent employed with CRISPR-Cas9, TALENS, or other approach protein visual reporters include green fluorescent proteins described herein based on production of double-strand breaks (e.g., GFP, GFP-2, tagGFP. turboGFP EGFP Emerald, or single-stranded nicks in the host cell. Azami Green, Monomeric Azami Green, CopGFP. AceGFP. I0134. In various embodiments, the guide RNAS or crR ZsGreen1), yellow fluorescent proteins (e.g. YFP, EYFP Cit NAs are elaborated with the approaches described above to rine, Venus, YPet, PhiYFP, ZsYellow 1), blue fluorescent pro create a library of different guide or crRNAs targeting differ teins (e.g. EBFP, EBFP2, AZurite, mKalama1, GFPuv, Sap ent genetic sequences to explore different efficiencies of tar phire, T-Sapphire), cyan fluorescent proteins (e.g. ECFP, geted cutting by the programmable nuclease. Alternatively or Cerulean, CyPet, AmCyan1, Midoriishi-Cyan), red fluores in addition, the DNA binding domain in TALEN restriction cent proteins (mKate, mKate2, mPlum, DSRed monomer, enzymes, or ZFNs, or Bulls is altered or modified by MAGE. mCherry, mRFP1, DsRed-Express, Dsked2, DSRed-Mono I0135) In these or other embodiments, PAM recognition mer, HcRed-Tandem, HcRed1, AsFed2, eqFP611, mRas sites for further engineering near the targeted locus is intro berry, mStrawberry, Jred), and orange fluorescent proteins duced with MAGE. If it is useful for a specific sequence to be (mCrange, mKO, Kusabira-Orange, Monomeric Kusabira cleaved by the Cas9 endonuclease, and there are no PAM Orange, mTangerine, tdTomato) or any other Suitable fluo recognition sites near this target, or if it desireable to avoid rescent protein. one, a new PAM recognition site may be introduced via 0128. In various embodiments, a protein may be fused to MAGE to enable CRISPR to function on a desired locus in the the tag through a peptide linker. The sequence of the linker genome. Similarly, PAM recognition sites may be ablated peptide is chosen based on known structural and conforma from a genomic sequence via MAGE. tional contributions of peptide segments to allow for proper 0.136. In some embodiments, the biomolecule of interest is folding and prevent possible steric hindrance of the protein to one or more RNA sequences, which may be altered to have be tagged and the tag polypeptide. Linker peptides are com optimal folding, stability or expression properties for thera monly used and known in the art, and may be from about 3 to peutic applications. The RNA sequence may be altered to about 40 amino acids in length. change its binding affinity, catalytic activity, or regulation of US 2016/01 86168 A1 Jun. 30, 2016 its message. For example, in the case of mRNAs, the mRNAs synthase, nopaline synthase, ubiquitin, Zein protein, and may also be altered to have reduced or increased recognition anthocyanin promoters (useful for expression in plant cells); efficiencies by host RNA-binding proteins or other host animal and mammalian promoters known in the art include, RNAs. In the case of mRNAs, the mRNAs may be altered to but are not limited to, the SV 40 early (SV 40e) promoter change translation of the message based on inter- or intra region, the promoter contained in the 3 long terminal repeat molecular interactions. RNAS that are designed to contain (LTR) of Rous sarcoma virus (RSV), the promoters of the unnatural or alternate chemistries may also be targeted by the EIA or major late promoter (MLP) genes of adenoviruses invention. (Ad), the cytomegalovirus (CMV) early promoter, the herpes 0.137 These strategies allow for a large variety of com simplex virus (HSV) thymidine kinase (TK) promoter, a pounds to be produced at higher levels (or other desired baculovirus IEI promoter, an elongation factor 1 alpha (EF1) phenotype associated with industrial production of chemi promoter, a phosphoglycerate kinase (PGK) promoter, a cals), and in diverse organisms. ubiquitin (Ube) promoter, an albumin promoter, the regula 0.138. Where the invention involves production of expres tory sequences of the mouse metallothionein-L promoter and sion constructs, exemplary regulatory regions that can be transcriptional control regions, the ubiquitous promoters included include, without limitation, promoter sequences, (HPRT, vimentin, a-actin, tubulin and the like), the promoters enhancer sequences, response elements, protein recognition of the intermediate filaments (desmin, neurofilaments, kera sites, inducible elements, protein binding sequences, 5' and 3' tin, GFAP, and the like), the promoters of therapeutic genes untranslated regions (UTRs), transcriptional start sites, ter (of the MDR, CFTR or factor VIII type, and the like), patho mination sequences, polyadenylation sequences, and introns. genesis or disease related-promoters, and promoters that Exemplary promoter sequences that can be used in the exhibit tissue specificity and have been utilized in transgenic expression constructs of the present invention include, e.g., animals, such as the elastase I gene control region which is promoter sequences capable of driving gene expression in active in pancreatic acinar cells; insulin gene control region target eukaryotic and/or prokaryotic cells. Specifically, con active in pancreatic beta cells, immunoglobulin gene control structs can include eukaryotic and prokaryotic promoters. An region active in lymphoid cells, mouse mammary tumor virus expression construct can include multiple copies of a single control region active in testicular, breast, lymphoid and mast promoter or different promoters, e.g., two or more promoters. cells; albumin gene, Apo AI and Apo AII control regions When two or more promoters are used in a single expression active in liver, alpha-fetoprotein gene control region active in construct, the promoters can be selected to yield optimal US 2008/0235816 AI liver, alpha I-antitrypsin gene control expression of the encoded nucleic acids. region active in the liver, beta-globin gene control region 0.139. In some instances, expression constructs can active in mycoid cells, myelin basic protein gene control include one or more prokaryotic promoter sequences and/or a region active in oligodendrocyte cells in the brain, myosin Shine-Dalgarno sequence. Typically, prokaryotic promoter light chain-2 gene control region active in skeletal muscle, sequences contain two short consensus sequences at positions and gonadotropic releasing hormone gene control region -10 and -35 upstream from the transcription initiation site. active in the hypothalamus, pyruvate kinase promoter, Villin Prokaryotic promoter sequences that may be useful in the promoter, promoter of the fatty acid binding intestinal pro present invention include, but are not limited to, T7, T3, and tein, promoter of the Smooth muscle cella-actin, and the like. T5 bacteriovirus promoter sequences. In addition, these expression sequences may be modified by 0140 Expression constructs can include one promoter per addition of enhancer or regulatory sequences and the like. nucleic acid (e.g., operatively linked to a therapeutic nucleic 0.142 Enhancer elements can increase transcription lev acid). Expression constructs containing more than one pro els. Enhancer generally refers to a sequence of DNA that moter can contain multiple copies of the same promoter and/ functions at no fixed distance from the transcription start site or different promoters. The choice of promoter or promoter and can be either 5' or 3' to the transcription unit. Furthermore, combinations can be optimized to yield the highest expres enhancers can be within an intron as well as within the coding sion level of the therapeutic nucleic acid of interest in the sequence itself. They are usually between 10 and 300 base target cell. pairs in length, and they function in cis. Enhancers usually 0141. The selected promoter will depend on the desired function to increase transcription from nearby promoters. host cell. For example, promoters include but not limited to: Enhancers can also contain response elements that mediate viral promoters, bacterial promoters, animal promoters, the regulation of transcription. Exemplary enhancers that can mammalian promoters, synthetic promoters, constitutive pro be included in the constructs disclosed hereincan include, but moters, tissue specific promoter, developmental specific pro are not limited to, enhancer elements encoded by hepatitis B moters, inducible promoters, light regulated promoters; virus, BK virus, polyoma virus, rous Sarcoma virus (RSV), CYCI, HIS3, GALI, GAL4, GALIO, ADHI, PGK, PHOS, moloney murine leukemia virus (M-MuDV), SV40, TT virus, GAPDH, ADCI, TRPI, URA3, LEU2, ENO, TPI, alkaline papilloma virus, and adenovirus. phosphatase promoters (useful for expression in Saccharo 0.143 Internal ribosomal entry site (IRES) elements are myces); AOXI promoter (useful for expression in Pichia); nucleotide sequences that allow for cap-independent transla b-lactamase, lac, ara, tet, trp, IPDIPR, T7, tac, and trc pro tion initiation in the middle of a messenger RNA (mRNA). moters (useful for expression in Escherichia coli); light regu IRES elements can be usefully inserted, e.g., into bicistronic lated-, seed specific-, pollen specific-, ovary specific-, patho expression constructs to Support the expression (translation) genesis or disease related-, cauliflower mosaic virus 35S, of a second therapeutic nucleic acid. IRES elements can be CMV 35S minimal, cassava vein mosaic virus (CsVMV), added intercistronicly to a construct to confer internal initia chlorophyll alb binding protein, ribulose 1.5-bisphosphate tion of translation of an mRNA product independent of a 5' carboxylase, shoot-specific, root specific, chitinase, stress cap. Exemplary IRES elements include those present in, e.g., inducible, rice tungro bacilliform virus, plant Superpromoter, picornavirus, poliovirus, encephalomyocarditis virus, foot potato leucine aminopeptidase, nitrate reductase, mannopine and-mouth disease virus, flavivirus, hepatitis C virus, pestivi US 2016/01 86168 A1 Jun. 30, 2016 92 rus, classical Swine fever virus, retrovirus, murine leukaemia ited to colE1/pMB1, oriC, floriV/oriS, oriN, oriT, oriH and virus, lentivirus, simian immunodeficiency virus, insect RNA oriL, p15A, pBR322, pSC101, R6K, RK2, RSF1010, virus, and cricket paralysis virus. cloDF13, colA, RSF1030, P1, rep/mob, puB110, pRO1600/ 0144 Polyadenylation signals are useful for the synthesis P. oriV, pWV0, 2 micron and CEN/ARS, and SV40. of mRNA. Three elements define the core polyadenylation 0150. In some instance, expression constructs can encode signal. (1) a hexanucleotide sequence AAUAAA found 10 to markers to facilitate selection of cells expressing the vector. 30 nucleotides upstream of the cleavage site, (2) a U-rich or Examples of selectable marker genes known and used in the GU-rich element located downstream of the cleavage site and art include: genes providing resistance to 5-Fluoro-2'-deox (3) the poly(A) site. Polyadenylation signals that can be use yuridine, 5-Fluoroorotic Acid, acetamide, amplicillin, biala ful include, e.g., the bovine growth hormone (BGH), herpes phos, bleomycin, carbenicillin, coefotaxime, ceftriaxone, simplex virus-TK (HSV-TK), rabbit B-globin, simian virus chloramphenicol, D-cycloserine, erythromycin, G418, gen 40 (SV40) late, hepatitis B virus (HBV), and human papil tamycin, herbicide, hygromycin, kanamycin, kasugamycin, loma virus (HPV) polyadenylation signals. nalidixic acid, neomycin, nourseothricin, puromycin, 0145 Transcription initiation factors are useful for tran rifampicin, spectinomycin, Streptomycin, Sulfonamide, tetra Scription. Transcription initiation factors can be included in cycline, triclosan, trimethroprim, Zeocin and the like; and the constructs described herein. Transcription initiation fac genes that are used as phenotypic markers, i.e., anthocyanin, tors include. e.g., TFII-I, eukaryotic initiation factor 4G ccdB, gatal, isopentanyl transferase gene, maZF, lacY, regu (eIF4G) and DAP5. latory genes, pir, pheS, rpsL, sacB, tetAR, tolC and the like. 0146 Kozak sequences are useful for promoting efficient Use of such resistance markers allows identification of a cell translation, for example in eukaryotic cells. A kozak consen when the cell is cultured under selective pressure (e.g., in the Sus sequence can be added to a expression vector to enhance presence of the antibiotic). Selectable markers can also the expression of the nucleic acid(s) of interest. Exemplary include nutritional and/or auxotrophic markers, for example, Kozak sequences include, for example, CCACCAUG (SEQ ade, arg, can, galK, his, met, phe, thr, thy A. leu, lys, proC, ID NO: 1) and CCACCAUGG (SEQID NO:2). pyrF, trp, tyr, ura. 0147 Shine-Dalgarno Sequences are useful for promoting 0151. In some instances expression constructs can encode, efficient translation, for example in prokaryotic cells. Shine in addition to the selectable markers, detection markers such Dalgarno Sequences are typically located 6-7 nucleotides as, for example, nucleic acids encoding enzymes and/or upstream from a start codon. The six-base consensus detectable proteins. In other instances, detectable markers sequence is, for example, AGGAGG (SEQID NO:3). may be included on separate vectors or may be chosen as 0148 Termination control regions, i.e., terminator or genomic regions of the target cell. Exemplary detectable polyadenylation sequences, may also be derived from various markers that can be encoded by vectors include, but are not genes native to the preferred hosts. Optionally, a termination limited to, chemiluminescent or fluorescent proteins, such as, site may be unnecessary. In a preferred embodiment of the for example, green fluorescent protein (GFP), enhanced invention, the termination control region can comprise or be green fluorescent protein (EGFP), Renilla Reniformis green derived from a synthetic sequence, synthetic polyadenylation fluorescent protein, GFPmut2, GFPuv4, yellow fluorescent signal, an SV40 late polyadenylation signal, an SV40 poly protein (YFP), enhanced yellow fluorescent protein (EYFP), adenylation signal, a bovine growth hormone (BGH) poly cyan fluorescent protein (CFP), enhanced cyan fluorescent adenylation signal, viral terminator sequences, or the like. protein (ECFP), enhanced blue fluorescent protein (EBFP), 0149. In some instances, expression constructs can citrine and red fluorescent protein from discosoma (dsRED), include species-specific DNA elements (e.g., flanking luciferase, rhodamine, fluorescein and the like. In certain sequences) to facilitate integration of the constructorportions other embodiments, the detectable marker is an enzyme. In thereof into the genome of target cells and/or to promote certain other embodiments, the detectable marker is a non episomal or plasmid maintenance (i.e., replication signals). essential gene that can be assayed rapidly for genetic varia Where integration is required, expression constructs can tion by qPCR. In certain other embodiments, the detectable include loXP sequences flanking the integrating DNA marker is a drug resistance marker or nutritional marker that sequence. Inclusion of Such sequences allows Subsequent can be readily assessed for functionality by reverse selection. removal (e.g., post-MAGE) of the integrated sequence from 0152. As used herein, a vector (or plasmid) refers to dis the genome via the standard practice of Creexpression, which crete elements that are used to, for example, introduce heter is transformed and expressed from a separate vector. Where ologous nucleic acid into cells for expression or replication episomal expression is required, expression constructs can thereof. The vectors can remain episomal or can be designed include species-specific origins of replication and one or to effect integration of a gene or portion thereof into a chro more selectable markers. In such cases, the episome can be mosome of the genome. Also contemplated are vectors that removed by discontinuing its selection. Exemplary origins of are artificial chromosomes, such as yeast artificial chromo replication Suitable for inclusion in the vectors are known in Somes and mammalian artificial chromosomes. Selection and the art (see, e.g., Bryant et al., J Exp. Bot., 52(355): 193-202 use of such vehicles are well knownto those of skill in the art. (2001); Edward et al., Basic Virology Third Edition, Black Included are vectors capable of expressing DNA that is opera well publishing, ISBN 1-4051-4715-6 (2007); Mott and tively linked with regulatory sequences, such as promoter Berger, Nat. Rev. Microbial., 5(5): 343-54 (2007); Huberman regions, that are capable of effecting expression of such DNA et al., Cell, 6: 51(3):473-81 (1987); Brewer and Fangman, fragments (e.g. expression vectors). Thus, a vector refers to a Cell, November 6:51(3):463-71 (1987); Kitai et al., J. Virol. recombinant DNA or RNA construct, such as a plasmid, a 79(10): 5933-5942 (2005); Kelman, Trends Microbiol. 12: phage, recombinant virus or other vector that, upon introduc 399-401 (2004); Nasheuer et al., Prog. Nucleic Acid Res. tion into an appropriate host cell, results in expression of the Mol. Biol., 72: 41-94 (2002); Cheuk et al., Nucl. Acids Res. DNA. Appropriate vectors are well known to those of skill in 40 (D1): D682-D686 (2012)). These include but are not lim the art and include those that are replicable in eukaryotic cells US 2016/01 86168 A1 Jun. 30, 2016

and/or prokaryotic cells and those that remain episomal or amp3: E. coli phage vector lambda BLUEMID-; E. coli those that integrate into the host cell genome. phage vector lambda BLUEMID+: E. coli phage vector 0153. In some embodiments, the present compositions lambda clKH100 (IS5); E. coli phage vector lambda DASH and methods can include vectors based and/or generated II: E. coli phage vector lambda DL10, E. coli phage vector using commercially available expression constructs, which lambda DL11, E. coli phage vector lambda DR2: E. coli can optionally be adapted or optimized for use in certain phage vector lambda ExCell: E. coli phage vector lambda species and/or cell types. Examples of Such expression con FIX II: E. coli phage vector lambda GEM11; E. coli phage structs include the GATEWAY cloning vector available from vector lambda GEM12, E. coli phage vector lambda GEM2; INVITROGEN, which is available for multiple species. E. coli phage vector lambda GEM4: E. coli phage vector Examples of other expression constructs Suitable for use in lambdagt10, E. coliphage vector lambdagt 102; E. coliphage various species are known in the art. By way of example, vector lambda gt11, E. coli phage vector lambda gt11D. E. expression constructs Suitable for use in, for example, Pichia coliphage vector lambdagt11 SciI/NotI: E. coliphage vector pastoris include, for example, paO815, pGAPZ, pGAPZa, lambdagt22A. E. coliphage vector lambdagtWES. lambdaE: pHIL-D2, pHIL-S1, pPIC3.5K, pPIC9K, pPICZ, and E. coliphage vector lambda gtWES.lambda B'; E. coliphage pPICZa. By way of example, expression constructs suitable vector lambda gtWES.T5-622; E. coli phage vector lambda for episomal maintenance in for example, Kluyveromyces MAX1; E. coli phage vector lambda MGU 1. E. coli phage lactis include, for example, pKD1. Expression constructs vector lambda MGU2: E. coli phage vector lambda N-cl857 Suitable for integration in Kluyveromyces lactis include, for r32; Vertebrate/E. coli phage vector lambda NMT. E. coli example, pGE-HSb20 vector (Swinkels et al. Antonie van phage vector lambda plac Mul, E. coli phage vector lambda Leeuwenhoek, 64:187-201 (1993); Bergkamp et al., Current placMu3: E. coliphage vector lambda pMu507: E. coli phage Genetics, 21 (4-5):365-370 (1992); Rossolini et al. Gene, 21; vector lambda pMu507.3: E. coli phage vector lambda 119(1):75-81 (1992); Domínguez et al., the Official Journal Pop 10, E. coli phage vector lambda Popó; E. coli phage of the Spanish Society for Microbiology, 1:131-142 (1998)). vector lambda SE4, E. coliphage vector lambda SE5 E. coli pKLAC1 or pKLAC2 (Paul A. Colussi and Christopher H. phage vector lambda SE6; E. coliphage lambdaSK17; E. coli Taron, Appl Environ Microbiol. 71 (11): 7092-7098 (2005)). phage lambdaSK20. E. coli phage lambdaSK22: E. coli 0154 The art provides a variety of vectors that find use in phage lambdaSK23: E. coli phage vector lambda SurfAAP: the present invention. By way of non-limiting illustration, E. coli phage vector lambda ZAP Express; E. coli phage phage vectors, plasmid vectors, phagemid vectors, phasmid vector lambda ZAPII:Vertebrate/E. coliphage vector lambda vectors, cosmid vectors, virus vectors and YAC vectors may ZD31; Vertebrate/E. coli phage vector lambda ZD32; Verte be used in the present invention. brate/E. coli phage vector lambda ZD35; E. coli phage vector 0155. In some embodiments, the following non-limiting lambda Ziplox; E. coli phage vector M13blað. E. coliphage illustrative phage vectors find use in the present invention: E. vector M13blacatl. E. coli phage vector M13Goril, E. coli coli phage vector lambda EMBL3 left arm: E. coli phage phage vector M13K07: E. coli phage M13mp7-14, E. coli vector lambda EMBL3 right arm; Bacteriophage fl; Bacte phage vector M13.SV.8, E. coli phage vector M13.SV.B11; riophage fa; E. coli phage vector fa strain 478; E. coli phage E. coli phage vector M13.SV.B12, E. coli phage vector vector fa-tet; E. coli phage vector fa fKN 16: E. coli phage M13tg103: E. coli phage vector M13tg114: E. coli phage vector fl IR1; E. coli phage vector lambda (Styloviridae); E. vector M13tg115; E. coli phage vector M13tg1 17: E. coli coli phage vector M13, E. coli phage vector M13BM20, E. phage vector M13um20; E. coli plasmid vector pPop 10; E. coli phage vector M13BM21, E. coli phage vector M13LH1. coli phage vector lambda Syrinx 2A; Streptomyces phage E. coli phage vector M13mc 18; E. coli phage vector vector TG1; and Streptomyces phage vector TG2. M13mIC7 E. coli phage vector M13mp1 E. coli phage 0156. In some embodiments, plasmid vectors find use in vector M13mp10; E. coli phage vector M13mp11. E. coli the present invention. In some embodiments the vectors of the phage vector M13mp18. E. coli phage vector M13mp19; E. present disclosure are useful in, by way of non-limiting coliphage vector M13mp2, E. coliphage vector M13mp7, E. example, E. coli. In some embodiments, the following illus coliphage vector M13mp8, E. coli phage vector M13mp9; E. trative plasmids may be used in E. coli (or other suitable cells, coli phage vector M13plex00, E. coli phage vector including those disclosed herein): CFSN1; Charon 4: EZ-Tn5 M13plex01; E. coli phage vector M13plex05; E. coli phage pMOD-2: EZ-Tn5 pMOD-3; EZ-Tn5 pMOD-4; EZ-Tn5 vector M13plex06: E. coli phage vector M13plex07: E. coli pMOD-5; LITMUS28i, LITMUS38i: p.ACYC177; phage vector M13plex 10: E. coliphage vector M13plex 13: E. pACYC184; p.ACYCDuet-1; p.AH153; p.ALTER-EX1; p.AL coli phage vector M13plex 17 E. coli phage vector TER-EX2: p416: p3AC-2cp; pBACgus-2cp; pBAD M13plex 18, E. coli phage vector M13plex 19, E. coli phage DEST49; pBAD-TOPO; pBAD-TOPO/Lacz; pBAD-TOPO/ vector M13plex20; E. coli phage vector M13tg130; E. coli Lacz/V5-His; pBAD/gIII A; p3AD/gIII B; pBAD/gIII C: phage vector M13tg131 E. coliphage vector M13 WB23, E. pBAD/gIII Calmodulin; pBAD/His A: pBAD/His B: pBAD/ coli phage vector M13WB2341, E. coli phage vector His C; pBAD/His/LacZ: pBAD/myc-His A: pBAD/myc-His M13 WB2342: E. coli phage vector M13 WB2344 or B; pBAD/myc-His C; pBAD/Myc-His/lacZ: pBAD/Thio: M13 WB2348; E. coli phage vector M13 PhageScript; E. coli pBAD/Thio-E: pBAD/Thio-TOPO; pBAD102/D-TOPO; plasmid vector pPop6 tim: E. coli phage vector fl R199, E. pBAD102/D/Lacz; pBAD18; pBAD18-Cm; pBAD18-Kan: coli phage vector fl R208; E. coli phage vector f1 R229; E. pBAD18s; pBAD202/D-TOPO; pBAD202/D/LacZ: coli phage vector lambda EMBL12, E. coli phage vector pBAD24; pBAD28; pBAD30; pBAD33; pBADX53; pBEc lambda EMBL3 Aam Bam: E. coli phage vector lambda Q: pBEc-SBP: pBEc-SBP-Q; pBEc-SBP-SET1: pBEc-SBP EMBL3 cos; E. coli phage vector lambda EMBL3-cos-Not; SET1-Q; pBEc-SBP-SET2: pBEc-SBP-SET2-Q; pBEc E. coli phage vector lambda EMBL4: E. coli phage vector fa SBP-SET3: pBEc-SBP-SET3-Q; pBEc-SET1: pBEc-SET2: fBH 16: E. coli phasmid phage vector lambda 1059: E. coli pBEc-SET3; pBEn-SBP-SET1a; pBEn-SBP-SET1b; pHEn phage vector lambda 2001; E. coli phage vector lambda SBP-SET1c; pBEn-SBP-SET2a: pBEn-SBP-SET2b: pBEn

US 2016/01 86168 A1 Jun. 30, 2016 coli phagemid vector pFL64; Saccharomyces/E. coli fl+, E. coli phagemid vectorpSP64 polyA. E. coli phagemid phagemid vectorpFL64+; E. coli phagemid vector pGEM-1 vector pSP65-fl+: E. coli phagemid vector pSP6-T3: E. coli E. coliphagemid vector pGEM-1Zf E. coli phagemid vector phagemid vector pSP6-T7-19, E. coli phagemid vector pGEM-1Zf-; E. coli phagemid vector pGEM-13Zf+: E. coli pSP70, E. coli phagemid vector pSP71; E. coli phagemid phagemid vector pGEM-2: E. coliphagemid vector pGEM-3; vector pSP72: E. coli phagemid vector pSP73: E. coli E. coliphagemid vector pGEM-3Zf E. coli phagemid vector phagemid vector pSPORT1. E. coli phagemid vector pGEM-3Zf-; E. coli phagemid vector pGEM-4: E. coli pSPORT2: E. coli phagemid vector pSPT18, E. coli phagemid vector pGEM-5Zf-; E. coli phagemid vector phagemid vector pSPT19: E. coli phagemid vector pGEM-7Zf E. coli phagemid vector pGEM-7Zf+: E. coli pSPTbm20; E. coli phagemid vector pSPTbm21; E. coli phagemid vector pGEM-9Zf E. coli phagemid vector phagemid vector pSS24; E. coli phagemid vector pSS25; E. pGEM-luc; E. coli phagemid vector pGEM-T. Broad host coli phagemid vector pSVK3, E. coli phagemid vector pSV range/E. coli plasmid vector pGhost4; Broad host range/E. SPORT1: E. coli phagemid vector pT3T7BM: E. coli coli plasmid vector pGhost5; Broad host range/E. coli plas phagemid vectorpT3T7-lac; E. coliphagemid vectorpT3T7 mid vector pGhostó: E. coliphagemid vector pGL2-Basic; E. luc; E. coli phagemid vector pT7-0, E. coli phagemid vector coliphagemid vectorpGL2-Enhancer, Cloning vector pGL3 pT7-1; E. coli phagemid vector pT7-2, E. coli phagemid Basic; Cloning vector pGL3-Control; Cloning vector pGL3 vector pT7SP6, E. coli phagemid vector pTT7T3-18, E. coli Enhancer; Cloning vector pGL3-Promoter, E. coli phagemid phagemid vector pT7T3-18D. E. coli phagemid vector vector pGUSN358-S: E. coli phagemid vector PhageScript pT7T3-18U: E. coli phagemid vector pT7T3-19: E. coli SK; E. coliphagemid vector pHphO: E. coliphagemid vector phagemid vector pT7T3-19U: E. coli phagemid vector pHph-1, E. coli phagemid vector pHph+1; E. coli phagemid pT7T3alpha-18, E. coli phagemid vector pT7T3alpha-19; vector plCEM19H; Ecoil phagemid vector plCEM19H+: E. Vertebrate/E. coli phagemid vector pTF1. E. coli phagemid coli phagemid vector plCEM19R. E. coli phagemid vector vector pTRXN; E. coli phagemid vector pTRXN+: E. coli pICEM19R+: Vertebrate/E. coli phagemid vector plFCAT1: phagemid vector pTZ18R. E. coli phagemid vector pTZ18U: E. coli phagemid vector pKK161-8. E. coli phagemid vector E. coli phagemid vector pTZ19R. E. coli phagemid vector pko: E. coli phagemid vector pKO-neo: E. coli phagemid pTZ19U: E. coli phagemid vector pTZSV28; E. coli vectorpKSM710; E. coliphagemid vector pKSM711; E. coli phagemid vector puC118; E. coli phagemid vector puC119; phagemid vector pKSM713: E. coli phagemid vector E. coli phagemid vector pUC12: E. coli phagemid vector pKSM715, E. coli phagemid vector pKUN9; E. coli pUC12c: E. coli phagemid vector puC13: E. coli phagemid phagemid vector pKUN9; E. coli phagemid vector pH1; E. vector puC13c., E. coli phagemid vector puC18; E. coli coli plasmid vectorpMAL-c E. coli plasmid vectorpMAL-c2 phagemid vector puC18c: Photinus pyralis puC18-lu E. coli plasmid vector pMAL-cRI E. coli plasmid vector ciferase: E. coli phagemid vector puC19, E. coli phagemid pMAL-p E. coli plasmid vector pMAL-p2 E. coli phagemid vector puC1918, E. coli phagemid vector pUC19c. E. coli vector pMEX5, E. coli phagemid vector pMEX6: E. coli phagemid vector puC3: E. coli phagemid vector puC4, E. phagemid vector pMEX7. E. coli phagemid vector coli phagemid vector puC5, E. coli phagemid vector pUC7; pNEB193: E. coli phagemid vector pCN163, E. coli E. coli phagemid vector puC7c; E. coli phagemid vector phagemid vector pPL-lambda; E. coli phagemid vector pRic pUC8; E. coli phagemid vector puC8-1; E. coli phagemid CMV; E. coli phagemid vector pRcRSV: E. coli phagemid vector puC8-2, E. coli phagemid vector pUC830; E. coli vector pRIT2T. Saccharomyces/E. coli phagemid vector phagemid vector puC8c: E. coli phagemid vector puC9; E. pRS200; Saccharomyces/E. coli phagemid vector pRS303, coli phagemid vector puC9-1. E. coli phagemid vector Saccharomyces/E. coli phagemid vector pRS304; Saccharo pUC9-2, E. coli phagemid vector puC9c; E. coli phagemid myces/E. coli phagemid vector pRS305, Saccharomyces/E. vector puC9tet; E. coli phagemid vector puCbm20 or coli phagemid vector pRS306; Saccharomyces/E. coli pUCPZ2, E. coli phagemid vector puCbm21; E. coli phagemid vector pRS313, Saccharomyces/E. coli phagemid phagemid vectorpUCGM; E. coli phagemid vector puCP18; vector pRS314; Saccharomyces/E. coli phagemid vector E. coli phagemid vector puCP20, E. coli phagemid vector pRS315, Saccharomyces/E. coli phagemid vector pRS316: pUCP22, E. coliphagemid vectorpUCP24. E. coli phagemid Saccharomyces/E. coli phagemid vector pRS403, Saccharo vector puCP26: E. coli phagemid vector pUR1, E. coli plas myces/E. coli phagemid vector pRS404; Saccharomyces/E. mid vector pWM521; Vertebrate/E. coli phagemid vector coli phagemid vector pRS405, Saccharomyces/E. coli pXPRS- or pcDpolyB: Vertebrate/E. coli phagemid vector phagemid vector pRS406; Saccharomyces/E. coli phagemid pXPRS+ or pcDpolyB+: E. coli phagemid vector pYES2: E. vector pRS413. Saccharomyces/E. coli phagemid vector coli phagemid vector pYESHis A. E. coli phagemid vector pRS414; Saccharomyces/E. coli phagemid vector pRS415, pYESHisB: E. coli phagemid vector pYESHisC; Saccharo Saccharomyces/E. coli phagemid vector pRS416: Saccharo myces/E. coliphagemidpAS1;Yeast/E. coliphagemid vector myces/E. coli phagemid vector pRS423, Saccharomyces/E. pAS2: Saccharomyces/E. coli phagemid vector p ASZ10 E. coli phagemid vector pRS424; Saccharomyces/E. coli coli phagemid vector pBGS130- E. coli phagemid vector phagemid vector pRS425, Saccharomyces/E. coli phagemid pBGS130+: E. coli phagemid vector pBGS131 - E. coli vector pRS426: E. coli phagemid vector pRSETA. E. coli phagemid vector pBGS131+: E. coli phagemid vector phagemid vector pRSETB; E. coli phagemid vector pBGS18- E. coli phagemid vector pBGS18+: E. coli pRSETC: Saccharomyces/E. coli phagemid vector pRSS56; phagemid vector pBGS 19- E. coli phagemid vector Cloning vector pSI: E. coli phagemid vector pSK222, E. coli pBGS19+, E. coli phagemid vector pBGS8- E. coli phagemid vectorpSK241. E. coliphagemid vectorpSL1180: phagemid vector pBI221; E. coli phagemid vector pBK E. coli phagemid vector pSL1190, E. coli phagemid vector CMV; E. coli phagemid vector pBK-RSV: Trypanosoma/E. pSL301: E. coli phagemid vector pSP18; E. coli phagemid coli phagemid vector pBNsp-Neo-Alpha; E. coli phagemid vector pSP19, E. coli phagemid vector pSP64; E. coli vector pCR-Script SK(+); E. coli phagemid vector phagemid vector pSP64-fl. E. coli phagemid vector pSP64 pDELTA2, E. coli phagemid vector p)K101; Saccharomy