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Session Abstracts In Natural Product Discovery and Development in the Genomic Era Sunday, January 21 12:00 PM - 6:00 PM Registration Grand Ballroom Foyer, lobby level 5:00 PM - 6:00 PM Keynote Speech: Nigel Mouncey, Director Joint Genome Institute "New Voyages to Explore the Natural Product Galaxy" Salons F-G, lobby level 6:00 PM - 7:00 PM Welcome Reception Salons A-E, lobby level 6:00 PM - 8:00 PM Session: PS1: Poster Session 1 Salons A-E, lobby level P1 Sonogashira diversification of unprotected halotryptophans, halotryptohan containing tripeptides; and generation of a new to nature bromo-natural product and its diversification in water C. Cartmell*, University of St. Andrews, Strathkinness, United Kingdom The blending together of synthetic chemistry and natural product biosynthesis provides a potentially powerful route to new natural product analogues2. Cystargamide is a structurally interesting lipo-depsi peptide containing a 5-hydroxy tryptophan as well as a 2, 3-epoxydecanoyl fatty acid chain3. We envisaged that by installing a sufficiently reactive handle (e.g. a C-Br bond) and developing compatible mild aqueous chemistries, biosynthesis of the halo-cystargamides and its subsequent chemical modification can be achieved. Precursor directed biosynthesis (PDB) provides a great potential for the production of new natural product analogues by exploiting the natural promiscuity of the enzymes involved in the biosynthesis of natural product. Using PDB method, we achieved the incorporation of various chloro/bromo-tryptophans and generated a series of halogenated analogues of cystargamide. 6- Br-cystargamide was subsequently diversified using aqueous cross coupling chemistries such as the Sonogashira reaction to obtain new derivatives of cystargamide. The installation of bromo/chloro handle also provided an excellent analytical handle for investigation of all metabolites by LC-MS/MS. With knowledge gained from the fragmentation of the natural cystargamide, we analysed the MSn data to identify and characterise the new natural products analogues produced via the Sonogashira reaction1. References 1. J. Corr, S. V. Sharma, C. Pubill-Ulldemolins, et al. Chem Sci., 8, 2039-2046, (2017) P3 Identification and functional analysis of the aspergillic acid gene cluster in Aspergillus flavus M. Lebar*, J. Cary, R. Majumdar, C. Carter-Wientjes, B. Mack and Q. Wei, USDA, New Orleans, LA, USA; V. Uka, University of Ghent, Ghent, Belgium; S. DeSaeger, University of Ghent, Gent, Belgium; J. Di Mavungu, University of Gent, Gent, Belgium Aspergillus flavus can colonize important food staples and produce aflatoxins, a group of toxic and carcinogenic secondary metabolites. In silico analysis of the A. flavus genome has revealed 56 gene clusters predicted to be involved in the biosynthesis of secondary metabolites. A. flavus secondary metabolites produced during infection of maize seed are of particular interest, especially with respect to their roles in the biology of the fungus. A predicted nonribosomal peptide synthetase-like (NRPS-like) gene, designated asaC (AFLA_023020), present in the uncharacterized A. flavus secondary metabolite gene cluster 11 was shown to be expressed during the earliest stages of maize kernel infection. Cluster 11 was shown to be composed of six additional genes encoding a number of putative decorating enzymes as well as a transporter and transcription factor. LC-MS analysis of extracts from knockout mutants of these genes showed that they were responsible for the synthesis of the previously characterized antimicrobial mycotoxin aspergillic acid. Extracts of the asaC mutant showed no production of aspergillic acid or its precursors. Knockout of the cluster P450 oxidoreductase afforded a pyrazinone metabolite, the aspergillic acid precursor deoxyaspergillic acid. The hydroxamic acid functional group in aspergillic acid allows the molecule to bind to iron resulting in the production of a red pigment in A. flavus previously identified as ferriaspergillin. We observed significantly less fungal growth on maize kernels infected with A. flavus ΔasaC compared to A. flavus control and are currently investigating the role aspergillic acid plays in maize kernel infection, possibly through iron sequestration. P5 Photoprotection of the potent polyene antibiotic Marinomycin C. Bailey*, J. Zarins-Tutt, M. Agbo, M. Gan, E. Abraham, R. Hamed and R. Goss, University of St Andrews, St Andrews, United Kingdom; A.D. Taboada and G. Mackenzie, Sporomex Ltd, Bridlington, United Kingdom; A. Evans, Queen's University, Kingston, ON, Canada Bioactive polyenes are abundant in nature showing a broad range of chemical diversity and biological activities. Despite the promising bioactivity of many isolated polyenes, the inherent instability of polyene systems towards photoisomerization continues to deter their development towards potential lead drug candidates. Marinomycin is a particularly noteworthy, but photolabile, polyene antibiotic with excellent activity against MRSA and VRSA.1 We envisaged that microencapsulating polyenes using a chemically inert, biocompatible, non-toxic natural polymers could be utilised to improve photostability and as a drug carrier. We have demonstrated a striking level of photoprotection (t1/2 extended from 8 seconds – 34 minutes, when exposed directly to 312 nm UV radiation at 48 W) using a natural biopolymer. Our results show promise for the clinical development and administration of polyenes, such as marinomycin, that would otherwise be too unstable to consider. Additionally a serendipitous discovery revealed that our biopolymer could be used to selectively extract culture broths containing marinomycin providing higher recovery than extraction with conventional XAD resins. References H. C. Kwon, C. A. Kauffman, P. R. Jensen and W. Fenical, J. Am. Chem. Soc., 2006, 128, 1622–1632. P7 Biochemical role of multicore precursor peptides in a RiPP pathway W. Gu*, D. Sardar and E. Schmidt, University of Utah, Salt Lake City, UT, USA Cyanobactin pathways are diversity-generating biosynthetic pathways that can process hypervariable substrates. Each cyanobactin precursor peptide contains multiple core sequences encoding different natural products, which is not common in RiPPs. The role of these multicore precursor peptides remains unclear. Preliminary in vivo data suggests that the cassette position influences the production yield. Here, we perform biochemical experiments that define the role of multiple cassettes in cyanobactin RiPP biosynthesis. Investigation of the mechanisms behind this recognition will help us better control cyanobactin production for potential therapeutic applications. P9 Biosynthetic and genome mining approaches to identify triazine containing natural products K. Almabruk* and B. Philmus, Oregon State University, Corvallis, OR, USA; M. Fenwick and S. Ealick, Cornell University, Ithaca, NY, USA Triazine containing natural products are of interest because of their attractive biological activities and the unique chemistry involved in their biosynthesis. One of the most studied examples is toxoflavin, which has been isolated from plant pathogenic strains of Burkholderia, and plays a key role in virulence. Genome mining has revealed that triazine natural product gene clusters are found in pseudomonads and actinobacteria suggesting that triazine-containing natural products are more prevalent than previously realized. In this study, we present our results from precursor labeling studies in an effort to shed light on the complex biosynthetic steps involved in forming the N-N-bond of the triazine moiety during toxoflavin biosynthesis. We also discuss the crystallographic and the in vitro characterization of two N- methyltransferases that use 1,6-didesmethyltoxoflavin (1,6-DDMT) as a substrate. P11 Metagenomics-guided natural product discovery and engineering in bacteria T. Shock, X. Yang*, D. Chandran, J. Shock, O. Liu and J. Kim, Radiant Genomics, Emeryville, CA, USA Metagenomics continues to play an increasingly important role in the discovery of natural products. With the combination of next-generation sequencing, bioinformatics, genetic engineering and natural product chemistry, previously-inaccessible chemical diversity in our environment are being gradually uncovered. These technologies also circumvent the constraints of traditional culture-based natural product discovery, allowing for targeted approaches in heterologous hosts. This work focuses on recent progress in pipeline development and process engineering in a startup-scale industrial setting. P13 Autometa: Automated extraction of microbial genomes from shotgun metagenomes I. Miller*, E. Rees, J. Ross, I. Miller, J. Baxa, J. Lopera, R. Kerby, F. Rey and J. Kwan, University of Wisconsin - Madison, Madison, WI, USA Culture-independent sequencing (metagenomics) is a powerful, high resolution technique enabling the study of microbial communities in situ. With modern sequencing technology and bioinformatics, individual genomes can be assembled and extracted directly from environmental samples containing complex microbial communities by a process known as metagenomic "binning." However, available binning programs suffer from methodological and practical shortcomings, such as the requirement of human pattern recognition, which is inherently unscalable, low-throughput, and poorly reproducible. Some methods also require the assembly of pooled samples, which can lead to poor assemblies in the case of inter-sample strain variability. We therefore devised a fully-automated pipeline,
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