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Lasso Peptides from Actinobacteria - Chemical Diversity and Ecological Role Jimmy Mevaere

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Lasso Peptides from Actinobacteria - Chemical Diversity and Ecological Role Jimmy Mevaere Lasso peptides from Actinobacteria - Chemical diversity and ecological role Jimmy Mevaere To cite this version: Jimmy Mevaere. Lasso peptides from Actinobacteria - Chemical diversity and ecological role. Biochemistry [q-bio.BM]. Université Pierre et Marie Curie - Paris VI, 2016. English. NNT : 2016PA066617. tel-01924455 HAL Id: tel-01924455 https://tel.archives-ouvertes.fr/tel-01924455 Submitted on 16 Nov 2018 HAL is a multi-disciplinary open access L’archive ouverte pluridisciplinaire HAL, est archive for the deposit and dissemination of sci- destinée au dépôt et à la diffusion de documents entific research documents, whether they are pub- scientifiques de niveau recherche, publiés ou non, lished or not. The documents may come from émanant des établissements d’enseignement et de teaching and research institutions in France or recherche français ou étrangers, des laboratoires abroad, or from public or private research centers. publics ou privés. Université Pierre et Marie Curie ED 227 : Sciences de la Nature et de l’Homme : écologie et évolution Unité Molécules de communication et Adaptation des Micro-organismes (MCAM) / Equipe Molécules de défense et de communication dans les écosystèmes microbiens (MDCEM) Lasso peptides from Actinobacteria Chemical diversity and ecological role Par Jimmy Mevaere Thèse de doctorat de biochimie et biologie moléculaire Présentée et soutenue publiquement le 14 novembre 2016 Devant un jury composé de : Véronique Monnet Directeur de recherche Rapporteur Jean-Luc Pernodet Directeur de recherche Rapporteur Jean-Michel Camadro Directeur de recherche Examinateur Marcelino T. Suzuki Professeur Examinateur Sergey B. Zotchev Professeur Examinateur Séverine Zirah Maître de conférences Directrice de thèse Yanyan Li Chargée de recherche Codirectrice de thèse Acknowledgements At first, I would like to thank Séverine Zirah and Yanyan Li, my PhD supervisor, and Prof. Sylvie Rebuffat for having entrusted me as a candidate for the PhD scholarship with my little knowledge of molecular microbiology and how to best achieve science. I must acknowledge them for their support and guidance. Thank you for giving me the opportunity to work in this unique place which is MNHN and MCAM research lab. I want to thanks the members and colleagues of the laboratory for the very useful helps they provided me during these three years and for the discussion: Didier, Bastien, Sebastien, Stéphane, Soizic, Caroline, Alain P, Carine, Christine, Michel, Isabelle, Arlette, Marie-lise, Alyssa, Jean, Amandine, Linda, Benjamin M, Alain B, Alexandre and Séverine A. Particular thanks go to Jean-baptiste Rioux who welcomed me so nicely and who teaches me the basis of molecular biology at the bench. I must acknowledge the work and the help of Haiyan Ma who preceded me and started the heterologous expression lasso peptides. I want to thanks Christophe Goulard who helped me a lot with the cultivation and the purification of those tricky lasso peptides while I was battling against Streptomyces sviceus morphologies. Many thanks to Adrienne for support, advice and discussion. Many thanks go to the student who came in Yanyan’s team, Hortense, Maylis, Saravanane, Andrea, Paul and Victor. I want to acknowledge the other student and post-doc from the lab, Mehdi, Agathe, Béatrice, Marine, Alison, Benjamin, Wei, Anaïs, Ambre, Margot, Anne, Frédéric, Mélanie, Johann, Sophie, Natacha and Clara. I must acknowledge Manon and Laura for their help in microbiology, Soraya for qPCR experiments, and Lionel and Arul for mass spectrometry experiments. Many thanks to Nora, Djena and Brice for their helps in administration matters. Finaly my thanks go to my friends and my family, in particular Ten, la Mére, le Frére, la Soeur, Clémence, Yves, Emmanuel, Bastien, Rémi, Erwan, Marion, Morgane, Matthieu, Ly, Christophe, Raphaël, Dara, Jérôme, Mickael, for their support (Wanna have a beer?), guidance (Don’t do PhD fool) and encouragement during the past three years, in particular through the most difficult phases of the project. I II Abbreviations ABC transporter ATP-binding cassette transporter ACN Acetonitrile ACP Acyl carrier protein ACT Actinorhodin AT Acyltransferase ATP Adenosine triphosphate BGC Biosynthetic gene cluster bp Base pair C Cytosine CDA Calcium-dependent antibiotics cDNA Complementary cDNA CoA Coenzyme A Dha 2,3-didehydroalanine DHB 2, 5-dihydroxybenzoic acid Dhb (Z)-2,3-didehydrobutyrine DMSO Dimethyl sulfoxide DNA Deoxyribonucleic acid Dnase Deoxyribonuclease dsDNA Double-stranded DNA DTT Dithiothreitol EDTA Ethylenediaminetetraacetic acid ESI Electrospray ionization FA Formic acid G Guanine GBAP Gelatinase biosynthesis-activating pheromone GlcNAc N-acetylglucosamine HCCA α-cyano-4-hydroxycinnamic acid HK Histidine kinase HPLC High-performance liquid chromatography HTH helix-turn-helix KS β-ketoacyl synthase Lan meso-lanthionine III LC-MS Liquid chromatography-mass spectrometry LP Lasso peptide MeLan 3-methyllanthionine MIC Minimal inhibitory concentration Mw Molecular weight NGS Next-generation sequencing NMR Nuclear magnetic resonance NRP Non-ribosomal peptide NRPS Non-ribosomal peptide synthase OCS One-component system OD Optical density PCR Polymerase chain reaction PKS Polyketide synthase PTM Post-translational modification qPCR Real-time quantitative polymerase chain reaction QS Quorum sensing Q-tof Quadrupole-time of flight RED Undecylprodigiosin RiPP Ribosomally synthesized and post-translationally modified peptide RNA Ribonucleic acid Rnase Ribonuclease rpm Revolutions per minute RR Response regulator rRNA Ribosomal ribonucleic acid RT-PCR Reverse transcription polymerase chain reaction SAM S-adenosylmethionine-dependent methyltransferase SARP Streptomyces antibiotic regulatory protein SDS Sodium dodecyl sulfate SEM Scanning electron microscopy SET SDS, EDTA, Tris buffer ssDNA Single-stranded DNA TCS Two-component system TE trishydroxyméthylaminométhane-EDTA Tm Melting temperature IV Table of contents Acknowledgements _________________________________________________________ I Abbreviations ____________________________________________________________ III Table of contents __________________________________________________________ V Figures __________________________________________________________________ IX Tables ___________________________________________________________________ XI List of Annexes _________________________________________________________ XIII Introduction ______________________________________________________________ 15 Literature review __________________________________________________________ 17 I. Microbial natural product discovery in the genomics era _____________________ 17 I.1. Diversity of microbial specialized metabolites _________________________ 17 I.2. From genes to molecules __________________________________________ 23 I.3. Streptomyces, a prolific metabolite producer ___________________________ 24 I.3.a. The life cycle of Streptomyces __________________________________ 26 I.3.b. Regulation of specialized metabolite biosynthesis in Streptomyces ______ 27 I.3.b.i Pathway-specific regulators __________________________________ 29 I.3.b.ii Pleiotropic regulators _______________________________________ 31 II. Ribosomally synthesized and post-translationally modified peptides ___________ 32 II.1. Diversity _______________________________________________________ 32 II.2. Lanthipeptides __________________________________________________ 34 II.2.a. Structure ___________________________________________________ 34 II.2.b. Biosynthesis ________________________________________________ 34 II.2.c. Classification ________________________________________________ 36 II.2.d. Biological activities __________________________________________ 36 II.3. Thiopeptides ____________________________________________________ 37 II.3.a. Structure ___________________________________________________ 37 II.3.b. Biosynthesis ________________________________________________ 37 II.3.c. Classification ________________________________________________ 38 II.3.d. Biological activities __________________________________________ 38 II.4. Lasso peptides __________________________________________________ 40 II.4.a. Diversity ___________________________________________________ 40 II.4.b. Discovery __________________________________________________ 45 II.4.c. Biosynthesis ________________________________________________ 47 II.4.c.i Gene cluster organization ____________________________________ 47 II.4.c.ii Maturation process _________________________________________ 49 II.4.c.iii Additional modifications ____________________________________ 50 II.4.d. Biological activities __________________________________________ 54 II.4.e. Bioengineering using lasso peptides ______________________________ 55 III. Ecological role of RiPPs ______________________________________________ 56 IV. Objectives of the thesis _______________________________________________ 60 Materials and methods _____________________________________________________ 63 I. Chemicals and biological materials _____________________________________ 63 V II. General DNA and microbiology methods_________________________________ 63 II.1. Purification of plasmids and cosmids ________________________________ 63 II.2. Isolation of genomic DNA _________________________________________ 64 II.3. General Polymerase Chain Reaction methods (PCR) ____________________ 64 II.4. Agarose gel electrophoresis ________________________________________ 65 II.5. General cloning procedure _________________________________________
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