DOCSLIB.ORG

Cyanobacterial Microcystins and Human Health : First Steps Towards A

Total Page：16

File Type：pdf, Size：1020Kb

Download full-text PDF Read full-text
Cyanobacterial Microcystins and Human Health : First Steps Towards A Cyanobacterial microcystins and human health – First steps towards a congener dependent risk assessment of microcystins Dissertation zur Erlangung des akademischen Grades eines Doktors der Naturwissenschaften (Dr.rer.nat.) vorgelegt von Altaner, Stefan an der Mathematisch-Naturwissenschaftliche Sektion Fachbereich Biologie Konstanz, 2019 Konstanzer Online-Publikations-System (KOPS) URL: http://nbn-resolving.de/urn:nbn:de:bsz:352-2-uajiqfo13z2m0 Tag der mündlichen Prüfung: 19.07.2019 1. Referent: Prof. Dr. Daniel R. Dietrich 2. Referent: Prof. Dr. Valentin Wittmann Für meine Familie. Angela, Bruno, Bernhard, Manuela und Marie. Wer immer liegen bleibt, liegt falsch. (Broilers – Stoßen wir an) Danksagung Danksagung Mein Dank gilt Daniel Dietrich für die Bereitstellung des Promotionsthemas, für die Unterstützung beim Schreiben verschiedener Stipendienanträge, für die fachlichen Diskussionen und für das Möglich-Machen meines Forschungsaufenthalts am Cawthron Institute in Neuseeland. Mein weiterer Dank gilt Valentin Wittmann für die Übernahme des Zweitgutachtens, aber auch für die Betreuung und Mitarbeit an mehreren Manuskripten. Danke auch an Aswin Mangerich für die Bereitschaft als Prüfungsvorsitzender bereit zu stehen und die Möglichkeit, meine UPLC-MS/MS-Arbeiten in der AG für Molekulare Toxikologie durchführen zu können. Besonderer Dank gilt der ganzen AG Dietrich! Danke an meine ‚Laborfrau‘ Heinke für all die fachlichen und nichtfachlichen Unterhaltungen, die mir die Zeit kurzweilig gemacht haben. Danke an Marci für die besten Protokolle. Ich habe mich immer gefreut, wenn ich etwas gemacht habe, dass du vor mir schon mal gemacht hast. Danke an Barbara und Phil für viele Stunden sportlicher Ertüchtigung und sonstiger Ablenkung vom Laboralltag. Danke an Kevin, Nadja, Feli und Lisanne für eine immer gute Atmosphäre in der AG. Danke an Sascha, Pia, Karin, Sabine und Alex für die ganze Arbeit im „Hintergrund“, die gemacht hat, dass die AG funktioniert. Weiterer Dank gilt allen Studenten, die ich betreuen durfte und die mir tatkräftig bei dieser Arbeit geholfen haben: Jahn, Felix, Regina, Eva, Kevin, Helena, Julia, Lisa, Michail. Ein spezielles Dankeschön soll hierbei Regina für die unzähligen Phosphatase-Assays gelten, Jahn für seine unglaubliche Eigeninitiative in einem Projekt, von dem ich eigentlich keine Ahnung hatte und Eva für all das Klonieren der widerspenstigen Phosphatasen. Auch möchte in den Mitarbeitern des Cawthron Instituts für die schöne Arbeitsatmosphäre im Institut danken und ganz speziell Jonathan Puddick, der sich die Zeit genommen hat, mich zu betreuen und mich in die Geheimnisse der UPLC-MS/MS-Analytik einzuweihen. Danke an Tabea Zubel, die in Konstanz immer für meine Fragen bezüglich UPLC- MS/MS ein offenes Ohr hatte. Darüber hinaus möchte ich allen Ko-Autoren der Paper und Manuskripte danken, die alle dazu beigetragen haben, diese Werke zu verbessern. Speziell sei hier Sabrina Jaeger erwähnt, die sich immer die Zeit nahm, um nochmal eine Berechnung laufen zu lassen. Ein weiterer spezieller Dank gilt der Arthur-und-Aenne-Feindt-Stiftung und all ihren Mitarbeitern für die finanzielle Unterstützung meinerseits und des ganzen Projektes. Ich bin I Danksagung sehr dankbar über die unkomplizierte Art und Weise und die Verlängerungen der Stipendienzeit! Zuletzt möchte ich den wichtigsten und herzlichsten Dank an meine Familie aussprechen, denen ich diese Arbeit widmen möchte. Danke Mama und Papa für die bedingungslose Unterstützung, nicht nur während des Studiums, sondern auch allem was davor war und noch kommen wird. Danke an Bernhard für alle Gespräche über Wissenschaft oder sonstiges. Du warst und bist mir ein Vorbild, wissenschaftlich, wie auch im „richtigen Leben“. Danke an Manu, ohne dich wäre ich nicht, was ich bin und nicht komplett. Danke für deine Liebe und deine Unterstützung, für das Ertragen meiner Launen, für die Motivation in jeder Lebenslage, für wunderschöne zwölfeinhalb Jahre (es mögen noch ganz, ganz, ganz, (…) ganz viele weitere folgen) und vor allem Danke dafür, dass du mir die kleine Marie geschenkt hast! „You are my lighthouse in the dark. I can see you from a thousand miles” (In Flames – Here until forever). Danke auch an Marie, die mich immer wieder motiviert hat, wenn ich mal wieder die Schnauze voll hatte vom Schreiben . II Table of content Table of content DANKSAGUNG I TABLE OF CONTENT III LIST OF FIGURES VII LIST OF TABLES VIII LIST OF SUPPLEMENTARY FIGURES IX LIST OF SUPPLEMENTARY TABLES IX ABBREVIATIONS XI ABSTRACT XVI ZUSAMMENFASSUNG XVIII 1. GENERAL INTRODUCTION 1 1.1 Cyanobacteria .............................................................................................................. 1 1.1.1 Ecology of cyanobacteria .............................................................................................. 1 1.1.2 Cyanotoxins ................................................................................................................... 2 1.2 Microcystin ................................................................................................................... 4 1.2.1 Chemical structure ......................................................................................................... 4 1.2.2 Biosynthesis of microcystins and ecological role .......................................................... 5 1.3 Toxicokinetics of microcystins .................................................................................... 7 1.4 Toxicodynamics of microcystins ............................................................................... 10 1.4.1 Excursus: The ser/thr-PPP family in mammals ........................................................... 10 1.4.2 Consequences of microcystin exposure ....................................................................... 12 1.4.3 Proposed interaction sites of PPPs and MCs and mechanism of inhibition ................ 14 1.5 Risk assessment for microcystins and case reports of (human) intoxications ...... 15 1.5.1 Risk assessment ........................................................................................................... 15 1.5.2 Case reports ................................................................................................................. 17 1.6 Detection methods for microcystins ......................................................................... 19 2. AIM OF THE THESIS 21 3. MANUSCRIPT I (MICROCYSTIN ADSORPTION TO LAB-WARE) 23 3.1 Abstract ...................................................................................................................... 23 3.2 Introduction ............................................................................................................... 24 3.3 Material and Methods ............................................................................................... 26 3.3.1 Reagents and Laboratory-Ware ................................................................................... 26 III Table of content 3.3.2 Production of Microcystin Congener Stock Solution .................................................. 26 3.3.3 Adsorption of Microcystins to Common Pipetting Laboratory-Ware in Non-Acidified and Acidified Solvents ................................................................................................. 27 3.3.4 Short-Term Storage in Glass or Polypropylene Vials ................................................. 27 3.3.5 Ultra-performance liquid Chromatography-Tandem Mass Spectrometry (UPLC- MS/MS) Detection of Microcystins ............................................................................. 27 3.3.6 Outlier Analysis ........................................................................................................... 28 3.3.7 Data Handling and Statistical Analyses ....................................................................... 28 3.4 Results ......................................................................................................................... 29 3.4.1 Adsorption of Microcystin Congeners to Polypropylene Pipette Tips in Aqueous and High-Percentage Methanol Solutions .......................................................................... 29 3.4.2 Effect of Methanol Concentration on the Adsorption of Selected Microcystins to Polypropylene Pipette Tips .......................................................................................... 31 3.4.3 Effect of Acidified Methanol Concentration on the Adsorption of Selected Microcystins (MC) to Polypropylene Pipette Tips ...................................................... 32 3.4.4 Adsorption of Selected Microcystins (MC) in Acidified and Non-Acidified Aqueous Solutions to Glass-Ware (Pasteur Pipettes) ................................................................. 33 3.4.5 Effect of Acidified Methanol Concentration on the Adsorption of Selected Microcystins to Glass-Ware (Pasteur Pipettes) ........................................................... 34 3.4.6 Short Term Storage of MC Solutions in Glass or Polypropylene Vials ...................... 35 3.5 Discussion ................................................................................................................... 36 3.6 Conclusions ................................................................................................................. 39 3.7 Supplementary material ............................................................................................ 41 3.8 Acknowledgements ...................................................................................................
Load more

Recommended publications
  • Serine Proteases with Altered Sensitivity to Activity-Modulating
    (19) & (11) EP 2 045 321 A2 (12) EUROPEAN PATENT APPLICATION (43) Date of publication: (51) Int Cl.: 08.04.2009 Bulletin 2009/15 C12N 9/00 (2006.01) C12N 15/00 (2006.01) C12Q 1/37 (2006.01) (21) Application number: 09150549.5 (22) Date of filing: 26.05.2006 (84) Designated Contracting States: • Haupts, Ulrich AT BE BG CH CY CZ DE DK EE ES FI FR GB GR 51519 Odenthal (DE) HU IE IS IT LI LT LU LV MC NL PL PT RO SE SI • Coco, Wayne SK TR 50737 Köln (DE) •Tebbe, Jan (30) Priority: 27.05.2005 EP 05104543 50733 Köln (DE) • Votsmeier, Christian (62) Document number(s) of the earlier application(s) in 50259 Pulheim (DE) accordance with Art. 76 EPC: • Scheidig, Andreas 06763303.2 / 1 883 696 50823 Köln (DE) (71) Applicant: Direvo Biotech AG (74) Representative: von Kreisler Selting Werner 50829 Köln (DE) Patentanwälte P.O. Box 10 22 41 (72) Inventors: 50462 Köln (DE) • Koltermann, André 82057 Icking (DE) Remarks: • Kettling, Ulrich This application was filed on 14-01-2009 as a 81477 München (DE) divisional application to the application mentioned under INID code 62. (54) Serine proteases with altered sensitivity to activity-modulating substances (57) The present invention provides variants of ser- screening of the library in the presence of one or several ine proteases of the S1 class with altered sensitivity to activity-modulating substances, selection of variants with one or more activity-modulating substances. A method altered sensitivity to one or several activity-modulating for the generation of such proteases is disclosed, com- substances and isolation of those polynucleotide se- prising the provision of a protease library encoding poly- quences that encode for the selected variants.
    [Show full text]
  • Designing Peptidomimetics
    CORE Metadata, citation and similar papers at core.ac.uk Provided by UPCommons. Portal del coneixement obert de la UPC DESIGNING PEPTIDOMIMETICS Juan J. Perez Dept. of Chemical Engineering ETS d’Enginyeria Industrial Av. Diagonal, 647 08028 Barcelona, Spain 1 Abstract The concept of a peptidomimetic was coined about forty years ago. Since then, an enormous effort and interest has been devoted to mimic the properties of peptides with small molecules or pseudopeptides. The present report aims to review different approaches described in the past to succeed in this goal. Basically, there are two different approaches to design peptidomimetics: a medicinal chemistry approach, where parts of the peptide are successively replaced by non-peptide moieties until getting a non-peptide molecule and a biophysical approach, where a hypothesis of the bioactive form of the peptide is sketched and peptidomimetics are designed based on hanging the appropriate chemical moieties on diverse scaffolds. Although both approaches have been used in the past, the former has been more widely used to design peptidomimetics of secretory peptides, whereas the latter is nowadays getting momentum with the recent interest in designing protein-protein interaction inhibitors. The present report summarizes the relevance of the information gathered from structure-activity studies, together with a short review on the strategies used to design new peptide analogs and surrogates. In a following section there is a short discussion on the characterization of the bioactive conformation of a peptide, to continue describing the process of designing conformationally constrained analogs producing first and second generation peptidomimetics. Finally, there is a section devoted to review the use of organic scaffolds to design peptidomimetics based on the information available on the bioactive conformation of the peptide.
    [Show full text]
  • Polyketide Synthase Gene Coupled to the Peptide Synthetase Module Involved in the Biosynthesis of the Cyclic Heptapeptide Microcystinl
    J. Biochem. 127, 779-789(2000) Polyketide Synthase Gene Coupled to the Peptide Synthetase Module Involved in the Biosynthesis of the Cyclic Heptapeptide Microcystinl Tomoyasu Nishizawa, Akiko Ueda, Munehiko Asayama,* Kiyonaga Fujii,•õ Ken-ichi Harada,i Kozo Ochi,•ö and Makoto Shirai*,•˜,2 * Division of Biotechnology, School ofAgriculture, Ibaraki University Ami , Ibaraki 300-0393; •õFaculty of Pharmacy, M eija University, Tempaku , Nagoya 468-8503, •öNational Food Research Institute, Tsukuba, Ibaraki 305-8642; and •˜ Gene Research Center, Ibaraki University, Ann, Ibaraki 300-0393 Received January 17, 2000; accepted February 11, 2000 The peptide synthetase gene operon, which consists of encyA, mcyB, and mcyC, for the activation and incorporation of the five amino acid constituents of microcystin has been identified [T. Nishizawa et al. (1999) J. Biochem. 126, 520-529] . By sequencing an addi tional 34 kb of DNA from microcystin-producing Microcystis aeruginosa K-139 , we identifi ed the residual microcystin synthetase gene operon, which consists of mcyD, mcyE, meyF, and mcyG, in the opposite orientation to the mcyABC operon. McyD consisted of two polyketide synthase modules, and McyE contained a polyketide synthase module at the N-terminus and a peptide synthetase module at the C-terminus. McyF was found to exhibit similarity to amino acid racemase. McyG consisted of a peptide synthetase mod ule at the N-terminus and a polyketide synthase at the C-terminus. The microcystin syn thetase gene cluster was conserved in another microcystin-producing strain, Microcystis sp. S-70, which produces Microcystin-LR, -RR, and -YR. Insertional mutagenesis of mcyA, mcyD, or meyE in Microcystis sp.
    [Show full text]
  • Interrupted Adenylation Domains: Unique Bifunctional Enzymes Involved in Nonribosomal Peptide Biosynthesis
    Natural Product Reports Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis Journal: Natural Product Reports Manuscript ID: NP-REV-09-2014-000120.R1 Article Type: Highlight Date Submitted by the Author: 12-Jan-2015 Complete List of Authors: Labby, Kristin; Beloit College, Chemistry Watsula, Stoyan; University of Michigan, Medicinal Chemistry Garneau-Tsodikova, Sylvie; University of Kentucky, Pharmaceutical Sciences Page 1 of 11NPR Natural Product Reports Dynamic Article Links ► Cite this: DOI: 10.1039/c0xx00000x www.rsc.org/xxxxxx HIGHLIGHT Interrupted adenylation domains: unique bifunctional enzymes involved in nonribosomal peptide biosynthesis Kristin J. Labby, a Stoyan G. Watsula,b and Sylvie Garneau-Tsodikova* c Received (in XXX, XXX) Xth XXXXXXXXX 20XX, Accepted Xth XXXXXXXXX 20XX 5 DOI: 10.1039/b000000x Covering up to 2014 Nonribosomal peptides (NRPs) account for a large portion of drugs and drug leads currently available in the pharmaceutical industry. They are one of two main families of natural products biosynthesized on megaenzyme assembly-lines composed of multiple modules that are, in general, each comprised of three 10 core domains and on occasion of accompanying auxiliary domains. The core adenylation (A) domains are known to delineate the identity of the specific chemical components to be incorporated into the growing NRPs. Previously believed to be inactive, A domains interrupted by auxiliary enzymes have recently been proven to be active and capable of performing two distinct chemical reactions. This highlight summarizes current knowledge on A domains and presents the various interrupted A domains found in a number of 15 nonribosomal peptide synthetase (NRPS) assembly-lines, their predicted or proven dual functions, and their potential for manipulation and engineering for chemoenzymatic synthesis of new pharmaceutical agents with increased potency.
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2006/0110747 A1 Ramseier Et Al
    US 200601 10747A1 (19) United States (12) Patent Application Publication (10) Pub. No.: US 2006/0110747 A1 Ramseier et al. (43) Pub. Date: May 25, 2006 (54) PROCESS FOR IMPROVED PROTEIN (60) Provisional application No. 60/591489, filed on Jul. EXPRESSION BY STRAIN ENGINEERING 26, 2004. (75) Inventors: Thomas M. Ramseier, Poway, CA Publication Classification (US); Hongfan Jin, San Diego, CA (51) Int. Cl. (US); Charles H. Squires, Poway, CA CI2O I/68 (2006.01) (US) GOIN 33/53 (2006.01) CI2N 15/74 (2006.01) Correspondence Address: (52) U.S. Cl. ................................ 435/6: 435/7.1; 435/471 KING & SPALDING LLP 118O PEACHTREE STREET (57) ABSTRACT ATLANTA, GA 30309 (US) This invention is a process for improving the production levels of recombinant proteins or peptides or improving the (73) Assignee: Dow Global Technologies Inc., Midland, level of active recombinant proteins or peptides expressed in MI (US) host cells. The invention is a process of comparing two genetic profiles of a cell that expresses a recombinant (21) Appl. No.: 11/189,375 protein and modifying the cell to change the expression of a gene product that is upregulated in response to the recom (22) Filed: Jul. 26, 2005 binant protein expression. The process can improve protein production or can improve protein quality, for example, by Related U.S. Application Data increasing solubility of a recombinant protein. Patent Application Publication May 25, 2006 Sheet 1 of 15 US 2006/0110747 A1 Figure 1 09 010909070£020\,0 10°0 Patent Application Publication May 25, 2006 Sheet 2 of 15 US 2006/0110747 A1 Figure 2 Ester sers Custer || || || || || HH-I-H 1 H4 s a cisiers TT closers | | | | | | Ya S T RXFO 1961.
    [Show full text]
  • Structural Characterization of Microcystins by LC/MS/MS Under
    J. Antibiot. 59(11): 710–719, 2006 THE JOURNAL OF ORIGINAL ARTICLE ANTIBIOTICS Structural Characterization of Microcystins by LC/MS/MS under Ion Trap Conditions Tsuyoshi Mayumi, Hajime Kato, Susumu Imanishi, Yoshito Kawasaki, Masateru Hasegawa, Ken-ichi Harada This article is dedicated in memory of Professor Kenneth L. Rinehart at the University of Illinois Received: May 16, 2006 / Accepted: November 2, 2006 © Japan Antibiotics Research Association Abstract LC/MS/MS under ion trap conditions was used cyclic peptide antibiotics such as bacitracin [1], colistin [2], to analyze microcystins produced by cyanobacteria. vancomycin [3] and micafungin [4], are widely used for Tandem mass spectrometry using MS2 was quite effective medical treatments. Moreover, cyclosporin [5] is an since ions arising from cleavage at a peptide bond provide immunosuppressive agent, which has been used for organ useful sequence information. The fragmentation was transplant rejection or bone marrow [6]. confirmed by a shifting technique using structurally-related For the structure determination of cyclic peptides, the microcystins and the resulting fragmentation pattern was following information is required: structures, absolute different from those determined by triple stage MS/MS and configurations and sequence of constituent amino acids. four sector MS/MS. Analysis of a mixture of microcystins Although partial acid hydrolysis had been used for the in a bloom sample was successfully performed and two structure determination of these cyclic peptides, it has been new microcystins were identified by LC/MS/MS under ion currently performed by instrumental methods such as 2D- trap conditions. Thus, LC/MS/MS under ion trap NMR (two dimensional nuclear magnetic resonance) and conditions is effective for the structural characterization of MS/MS (tandem mass spectrometry) techniques.
    [Show full text]
  • Microcystin-LR Toxicodynamics, Induced Pathology, and Immunohistochemical Localization in Livers of Blue-Green Algae Exposed Rainbow Trout (Oncorhynchus Mykiss)
    Microcystin-LR Toxicodynamics, Induced Pathology, and Immunohistochemical Localization in Livers of Blue-Green Algae Exposed Rainbow Trout (Oncorhynchus mykiss) W. J. Fischer,* B. C. Hitzfeld,* F. Tencalla,† J. E. Eriksson,‡ A. Mikhailov,‡ and D. R. Dietrich*,1 *Environmental Toxicology, University of Konstanz, Konstanz, Germany; †Institute of Toxicology, Schwerzenbach, Switzerland; and ‡Turku Centre for Biotechnology, Turku, Finland Received June 29, 1999; accepted September 27, 1999 Microcystins (MC) constitute a family of toxins that are With this retrospective study, we investigated the temporal produced by several cyanobacterial taxa. These cyclic hep- pattern of toxin exposure and pathology, as well as the topical tapeptide molecules contain both L- and D-amino acids and an relationship between hepatotoxic injury and localization of micro- unusual hydrophobic C D-amino acid commonly termed cystin-LR, a potent hepatotoxin, tumor promoter, and inhibitor of 20 protein phosphatases-1 and -2A (PP), in livers of MC-gavaged ADDA (3-amino-9-methoxy-2,6,8-trimethyl-10-phenyldeca- rainbow trout (Oncorhynchus mykiss) yearlings, using an immu- 4,6-dienoic acid). In most of the more-than-60 presently known nohistochemical detection method and MC-specific antibodies. toxin congeners, the 5 D-amino acid components are main- H&E stains of liver sections were used to determine pathological tained while the two L-amino acids are variable (Botes et al., changes. Nuclear morphology of hepatocytes and ISEL analysis 1985). Microcystin-LR, containing L-Leu and L-Arg, is one of were employed as endpoints to detect the advent of apoptotic cell the most commonly occurring (Watanabe et al., 1996) and at death in hepatocytes.
    [Show full text]
  • A Metagenomic Insight Into the Role Of
    A METAGENOMIC INSIGHT INTO THE ROLE OF WASTEWATER TREATMENT PLANTS AS POTENTIAL HOTSPOT FOR ANTIBIOTIC RESISTANT BACTERIA AND ANTIBIOTIC RESISTANCE GENES by PO-CHENG TANG Submitted in fulfilment of the academic requirements for the degree of Master of Science (MSc) in the Discipline of Microbiology, School of Life Sciences, College of Agriculture, Engineering and Science at the University of KwaZulu-Natal, Durban, South Africa. June 2016 As the candidate’s supervisor, I have approved this dissertation for submission. Name: ____________________Prof. A. O. Olaniran Signed: ____________________ Date: _______________ i Abstract The magnitude of the global freshwater crisis is underestimated. Although international and national efforts have implemented strategies to safeguard these precious resources, the consequential effect of continued deterioration of water quality on the available options for water usage is still a major area of concern. Contamination of surface water resources resulting from inadequate treated effluent discharge from wastewater treatment plants (WWTPs) has previously been indicated as an important topic requiring continued investigations. Often, these discharges introduce large amounts of organic matter and nutrients which could lead to eutrophication and temporary oxygen deficiencies, ultimately disrupting the natural biotic community structure and its important ecological functions. In addition, pathogenic bacteria and antibiotic resistance genes (ARGs) present in the wastewater discharged increases public health risks due to their disease causing potential and dissemination of resistance determinants, respectively. This could result in increased cases of diseases such as dysentery, cholera, skin infections and typhoid, leading to higher rates of mortality and morbidity, placing further stresses on the public health system. Hence, better management and minimisation of microbial pathogens and antibiotic resistant bacteria in WWTPs is crucial to prevent the dissemination of potential pathogens and ARGs into the environment.
    [Show full text]
  • Affy ID Fold Change P-Value Realtive Change Annotation Derivation
    Supplemental Table 2: Gene changes at 60 minutes in adherent versus non-adherent samples Affy_ID Fold change p-value Realtive_change Annotation Derivation of annotation A4052_s_at 4.313332633 0.024012538 Increase_in_Adherent trpE; anthranilate synthase component I (EC:4.1.3.27); K01657 anthranilate synthase component I [EC:4.1.3.27] ecw:EcE24377A_1463 V1799_s_at 3.972247924 0.033307448 Increase_in_Adherent hscB; co-chaperone HscB ; K04082 molecular chaperone HscB sdy:SDY_2723 V0231_s_at 3.95580421 0.000284517 Increase_in_Adherent ssb; single-stranded DNA-binding protein ; K03111 single-strand DNA-binding protein sdy:SDY_4508 SB5_0275_s_at 3.893614168 1.07E-05 Increase_in_Adherent hypothetical protein ; K02040 phosphate transport system substrate-binding protein sbo:SBO_3421 K3820_x_at 3.763692747 7.60E-05 Increase_in_Adherent putative holin protein eoj:ECO26_3693 O2ColV121_at 3.647435418 2.22E-05 Increase_in_Adherent NO_KEGG_DATA NO_KEGG_DATA SD1_2456_x_at 3.566304619 0.015156769 Increase_in_Adherent putative fructose-like phosphotransferase EIIB subunit 3 ; K11202 PTS system, fructose-specific IIB-like component [EC:2.7.1.69] sbc:SbBS512_E4440 SDY_4180_x_at 3.540687986 4.18E-05 Increase_in_Adherent NO_KEGG_DATA NO_KEGG_DATA D1328_s_at 3.533442346 0.004222188 Increase_in_Adherent NO_KEGG_DATA NO_KEGG_DATA A0552_s_at 3.51323466 0.019815913 Increase_in_Adherent hscB; co-chaperone HscB ; K04082 molecular chaperone HscB sdy:SDY_2723 b3350_s_at 3.455476842 0.000165312 Increase_in_Adherent NO_KEGG_DATA NO_KEGG_DATA V0624_x_at 3.388319399 0.000108353
    [Show full text]
  • (12) Patent Application Publication (10) Pub. No.: US 2016/0186168 A1 Konieczka Et Al
    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 &&&&3&&3&&**??*,º**)..,.: ××××××××××××××××××××-************************** Patent Application Publication Jun. 30, 2016 Sheet 3 of 4 US 2016/O186168 A1 No.vaegwzºkgwaewaeg Patent Application Publication Jun. 30, 2016 Sheet 4 of 4 US 2016/O186168 A1 US 2016/01 86168 A1 Jun.
    [Show full text]
  • A Mini Review on Microcystins and Bacterial Degradation
    toxins Review A Mini Review on Microcystins and Bacterial Degradation Isaac Yaw Massey and Fei Yang * Department of Occupational and Environmental Health, Xiangya School of Public Health, Central South University, Changsha 410078, China; [email protected] * Correspondence: [email protected] Received: 26 March 2020; Accepted: 11 April 2020; Published: 21 April 2020 Abstract: Microcystins (MCs) classified as hepatotoxic and carcinogenic are the most commonly reported cyanobacterial toxins found in the environment. Microcystis sp. possessing a series of MC synthesis genes (mcyA-mcyJ) are well documented for their excessive abundance, numerous bloom occurrences and MC producing capacity. About 246 variants of MC which exert severe animal and human health hazards through the inhibition of protein phosphatases (PP1 and PP2A) have been characterized. To minimize and prevent MC health consequences, the World Health Organization proposed 1 µg/L MC guidelines for safe drinking water quality. Further the utilization of bacteria that represent a promising biological treatment approach to degrade and remove MC from water bodies without harming the environment has gained global attention. Thus the present review described toxic effects and bacterial degradation of MCs. Keywords: microcystins; toxicity and carcinogenicity; bacterial degradation; degrading mechanism Key Contribution: The review highlights toxicity and carcinogenicity of microcystins and will further expand reader’s knowledge on bacterial degradation of these toxins. 1. Introduction Cyanobacteria are organisms that inhabit surface and bottom water. These organisms can accumulate to form blooms and scums which are mostly found on the water surface. WHO [1] reported that blooms of toxic cyanobacteria are gradually increasing worldwide in both frequency and severity.
    [Show full text]
  • Protein-Reactive Natural Products Carmen Drahl, Benjamin F
    Reviews B. F. Cravatt, E. J. Sorensen, and C. Drahl DOI: 10.1002/anie.200500900 Natural Products Chemistry Protein-Reactive Natural Products Carmen Drahl, Benjamin F. Cravatt,* and Erik J. Sorensen* Keywords: enzymes · inhibitors · molecular probes · natural products · structure– activity relationships Angewandte Chemie 5788 www.angewandte.org 2005 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim Angew. Chem. Int. Ed. 2005, 44, 5788 – 5809 Angewandte Enzyme Inhibitors Chemie Researchers in the post-genome era are confronted with the daunting From the Contents task of assigning structure and function to tens of thousands of encoded proteins. To realize this goal, new technologies are emerging 1. Introduction 5789 for the analysis of protein function on a global scale, such as activity- 2. Natural Products that Target based protein profiling (ABPP), which aims to develop active site- Catalytic Nucleophiles in directed chemical probes for enzyme analysis in whole proteomes. For Enzyme Active Sites 5790 the pursuit of such chemical proteomic technologies, it is helpful to derive inspiration from protein-reactive natural products. Natural 3. Natural Products that Target Non-Nucleophilic Residues in products use a remarkably diverse set of mechanisms to covalently Enzyme Active Sites 5794 modify enzymes from distinct mechanistic classes, thus providing a wellspring of chemical concepts that can be exploited for the design of 4. Targeting Nonenzymatic active-site-directed proteomic probes. Herein, we highlight several Proteins 5802 examples of protein-reactive natural products and illustrate how their 5. Summary and Outlook 5803 mechanisms of action have influenced and continue to shape the progression of chemical proteomic technologies like ABPP. 1.
    [Show full text]