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Accueil > Départements > Microbiologie > Sylvie LAUTRU : Microbiologie moléculaire des Actinomycètes

Publications de l’équipe


  • C. Aubry, J. - L. Pernodet, et S. Lautru, « A set of modular and integrative vectors for synthetic biology in Streptomyces », Applied and Environmental Microbiology, vol. 85, nᵒ 16, juin 2019.
    Résumé : With the development of synthetic biology in the field of (actinobacteria) specialized metabolism, new tools are needed for the design or refactoring of biosynthetic gene clusters. If libraries of synthetic parts (such as promoters or ribosome binding sites) and DNA cloning methods have been developed, to our knowledge, not many vectors designed for the flexible cloning of biosynthetic gene clusters have been constructed.We report here the construction of a set of 12 standardized and modular vectors designed to afford the construction or the refactoring of biosynthetic gene clusters in Streptomyces species, using a large panel of cloning methods. Three different resistance cassettes and four orthogonal integration systems are proposed. In addition, FRT sites were incorporated to allow the recycling of antibiotic markers and to limit the risks of unwanted homologous recombination in Streptomyces strains, when several vectors are used. The functionality and proper integration of the vectors in three commonly used Streptomyces strains, as well as the functionality of the Flp-catalysed excision were all confirmed.To illustrate some possible uses of our vectors, we refactored the albonoursin gene cluster from Streptomyces noursei using the Biocrick assembly method. We also used the seamless Ligase Chain Reaction cloning method to assemble a transcription unit in one of the vectors and genetically complement a mutant strain.IMPORTANCE One of the strategies employed today to obtain new bioactive molecules with potential applications for human health (for example antimicrobial or anticancer agents) is synthetic biology. Synthetic biology is used to biosynthesize new unnatural specialized metabolites, or to force the expression of otherwise silent natural biosynthetic gene clusters. To assist the development of synthetic biology in the field of specialized metabolism, we constructed and are offering to the community a set of vectors that were intended to facilitate DNA assembly and integration in actinobacteria chromosome. These vectors are compatible with various DNA cloning and assembling methods. They are standardized and modular, allowing the easy exchange of a module by another one of the same nature. Although designed for the assembly or the refactoring of specialized metabolite gene clusters, they have a broader potential utility, for protein production or genetic complementation, for example.
    Mots-clés : ACTINO, MICROBIO.

  • S. Najah, C. Saulnier, J. - L. Pernodet, et S. Bury-Moné, « Design of a generic CRISPR-Cas9 approach using the same sgRNA to perform gene editing at distinct loci », BMC biotechnology, vol. 19, nᵒ 1, p. 18, mars 2019.
    Résumé : BACKGROUND: The CRISPR/Cas (clustered regularly interspaced short palindromic repeat and CRISPR-associated nucleases) based technologies have revolutionized genome engineering. While their use for prokaryotic genome editing is expanding, some limitations remain such as possible off-target effects and design constraints. These are compounded when performing systematic genome editing at distinct loci or when targeting repeated sequences (e.g. multicopy genes or mobile genetic elements). To overcome these limitations, we designed an approach using the same sgRNA and CRISPR-Cas9 system to independently perform gene editing at different loci. RESULTS: We developed a two-step procedure based on the introduction by homologous recombination of 'bait' DNA at the vicinity of a gene copy of interest before inducing CRISPR-Cas9 activity. The introduction of a genetic tool encoding a CRISPR-Cas9 complex targeting this 'bait' DNA induces a double strand break near the copy of interest. Its repair by homologous recombination can lead either to reversion or gene copy-specific editing. The relative frequencies of these events are linked to the impact of gene editing on cell fitness. In our study, we used this technology to successfully delete the native copies of two xenogeneic silencers lsr2 paralogs in Streptomyces ambofaciens. We observed that one of these paralogs is a candidate-essential gene since its native locus can be deleted only in the presence of an extra copy. CONCLUSION: By targeting 'bait' DNA, we designed a 'generic' CRISPR-Cas9 toolkit that can be used to edit different loci. The differential action of this CRISPR-Cas9 system is exclusively based on the specific recombination between regions surrounding the gene copy of interest. This approach is suitable to edit multicopy genes. One such particular example corresponds to the mutagenesis of candidate-essential genes that requires the presence of an extra copy of the gene before gene disruption. This opens new insights to explore gene essentiality in bacteria and to limit off-target effects during systematic CRISPR-Cas9 based approaches.
    Mots-clés : ACTINO, Bait DNA, CRISPR-Cas9, deletions, dna, Essential gene, Foreign DNA, Generic tool, Lsr2, MICROBIO, Multicopy gene, Nucleoid-associated proteins, Streptomyces, Xenogeneic silencers.


  • W. Briand, O. Dao, G. Garnier, R. Guegan, B. Marta, C. Maupu, J. Miesch, K. Papadopoulo, A. Radoux, J. Rojahn, Y. Zhu, C. Aubry, P. Bouloc, S. Bury-Moné, A. Ferré, S. Lautru, O. Namy, et M. Sabeti-Azad, « Dégradation d’un anticancéreux dans les eaux usées - Une médaille d’or pour l’équipe GO Paris-Saclay », Medecine Sciences: M/S, vol. 34, nᵒ 12, p. 1111-1114, déc. 2018.
    Résumé : iGEM (pour <i>international genetically engineered machine)<i/> est un concours international autour de la biologie synthétique réunissant des étudiants de toutes disciplines (mathématiques, physique, biologie, arts, etc.). « L’objectif est de construire un système biologique fonctionnel complexe, en assemblant des composants individuels moléculaires simples et standardisés (fragments d’ADN), appelés « briques biologiques » (biobriques), sorte de « legos » moléculaires, entreposés au MIT (<i>Massachusetts Institute of Technology<i/>) (le <i>registry of standard biological parts<i/> contient environ 20 000 biobriques). C’est une démarche proche de celle de l’ingénieur qui assemble des circuits électroniques ». En 2004, lors de sa création par le MIT (<b>→<b/>), la compétition iGEM regroupait une quarantaine de projets ; 14 ans plus tard, elle accueille 350 équipes (6 000 étudiants, avec leurs instructeurs) issues des universités du monde entier. Elle culmine en un <i>Giant Jamboree<i/> de quatre jours à Boston en novembre, au cours duquel les équipes présentent leur projet. Le « wiki » de la compétition ( présente l’ensemble des projets ainsi que le palmarès. Cette année, ont été décernées 114 médailles d’or, 68 d’argent et 107 de bronze. Neuf équipes françaises étaient engagées.<b>(→) Voir l’article de J. Peccoud et L. Coulombel, dont certains passages sont repris dans ce « chapo », m/s n° 5, mai 2007, page 551<b/>
    Mots-clés : ACTINO, Animals, Antineoplastic Agents, Biodegradation, Environmental, Bioreactors, CHERDIR, DBG, Escherichia coli, Escherichia coli Proteins, gamma-Glutamyl Hydrolase, GST, Humans, I2BC, Metabolic Engineering, Methotrexate, MICROBIO, Multienzyme Complexes, Organisms, Genetically Modified, Peptide Synthases, RNASTR, SRRB, Waste Water, Water Pollutants, Chemical, Water Purification.
    Pièce jointe Full Text PDF 1.5 Mo (source)
    Pièce jointe Full Text PDF 1.5 Mo (source)

  • M. Gondry, I. B. Jacques, R. Thai, M. Babin, N. Canu, J. Seguin, P. Belin, J. - L. Pernodet, et M. Moutiez, « A Comprehensive Overview of the Cyclodipeptide Synthase Family Enriched with the Characterization of 32 New Enzymes », Frontiers in Microbiology, vol. 9, p. 46, 2018.
    Résumé : Cyclodipeptide synthases (CDPSs) use as substrates two amino acids activated as aminoacyl-tRNAs to synthesize cyclodipeptides in secondary metabolites biosynthetic pathways. Since the first description of a CDPS in 2002, the number of putative CDPSs in databases has increased exponentially, reaching around 800 in June 2017. They are likely to be involved in numerous biosynthetic pathways but the diversity of their products is still under-explored. Here, we describe the activity of 32 new CDPSs, bringing the number of experimentally characterized CDPSs to about 100. We detect 16 new cyclodipeptides, one of which containing an arginine which has never been observed previously. This brings to 75 the number of cyclodipeptides formed by CDPSs out of the possible 210 natural ones. We also identify several consensus sequences related to the synthesis of a specific cyclodipeptide, improving the predictive model of CDPS specificity. The improved prediction method enables to propose the main product synthesized for about 80% of the CDPS sequences available in databases and opens the way for the deciphering of CDPS-dependent pathways. Analysis of phylum distribution and predicted activity for all CDPSs identified in databases shows that the experimentally characterized set is representative of the whole family. Our work also demonstrates that some cyclodipeptides, precursors of diketopiperazines with interesting pharmacological properties and previously described as being synthesized by fungal non-ribosomal peptide synthetases, can also be produced by CDPSs in bacteria.
    Mots-clés : ACTINO, activity prediction, BIOSYN, Biosynthetic Pathways, MICROBIO, Secondary metabolites.

  • A. - S. L'Honneur, H. Leh, F. Laurent-Tchenio, U. Hazan, F. Rozenberg, et S. Bury-Moné, « Exploring the role of NCCR variation on JC polyomavirus expression from dual reporter minicircles », PloS One, vol. 13, nᵒ 6, p. e0199171, 2018.
    Résumé : JC virus (JCV), a ubiquitous human polyomavirus, can cause fatal progressive multifocal leukoencephalopathy (PML) in immune compromised patients. The viral genome is composed of two conserved coding regions separated by a highly variable non-coding control region (NCCR). We analyzed the NCCR sequence from 10 PML JCV strains and found new mutations. Remarkably, the NCCR f section was mutated in most cases. We therefore explored the importance of this section in JCV expression in renal (HEK293H) and glioblastoma (U-87MG) cell lines, by adapting the emerging technology of DNA minicircles. Using bidirectional fluorescent reporters, we revealed that impaired NCCR-driven late expression in glioblastoma cells was restored by a short deletion overlapping e and f sections. This study evidenced a relevant link between JCV NCCR polymorphism and cell-type dependent expression. The use of DNA minicircles opens new insights for monitoring the impact of NCCR variation.
    Mots-clés : ACTINO, MICROBIO.


  • S. Bury-Moné et B. Sclavi, « Stochasticity of gene expression as a motor of epigenetics in bacteria: from individual to collective behavior », Research in Microbiology, avr. 2017.
    Résumé : Measuring gene expression at the single cell and single molecule level has recently made possible the quantitative measurement of stochasticity of gene expression. This enables identification of the probable sources and roles of noise. Stochastic gene expression can result in bacterial population heterogeneity, offering specific advantages for fitness and survival in various environments. This trait is therefore selected during the evolution of the species, and is consequently regulated by specific genetic network architecture. Examples exist in stress-response mechanisms, as well as in infection and pathogenicity strategies, pointing to advantages for multicellularity of bacterial populations.
    Mots-clés : ACTINO, Behavior, Bi-stability, Epigenetics, gene expression, MICROBIO, Multicellularity, regulatory networks, Stochasticity.

  • D. Haas, C. Gerbaud, N. Sahin, J. - L. Pernodet, et S. Lautru, « Draft Genome Sequence of Streptomyces sp. M1013, a Close Relative of Streptomyces ambofaciens and Streptomyces coelicolor », Genome Announcements, vol. 5, nᵒ 29, juill. 2017.
    Résumé : We report the draft genome sequence of Streptomyces sp. M1013, a strain isolated from the Medicago arborea rhizosphere in Izmir, Turkey. An average nucleotide identity (ANI) analysis reveals that this strain belongs to the same species as Streptomyces canus ATCC12647 and is closely related to Streptomyces ambofaciens and Streptomyces coelicolor.
    Mots-clés : ACTINO, MICROBIO.

  • H. Leh, A. Khodr, M. - C. Bouger, B. Sclavi, S. Rimsky, et S. Bury-Moné, « Bacterial-Chromatin Structural Proteins Regulate the Bimodal Expression of the Locus of Enterocyte Effacement (LEE) Pathogenicity Island in Enteropathogenic Escherichia coli », mBio, vol. 8, nᵒ 4, août 2017.
    Résumé : In enteropathogenic Escherichia coli (EPEC), the locus of enterocyte effacement (LEE) encodes a type 3 secretion system (T3SS) essential for pathogenesis. This pathogenicity island comprises five major operons (LEE1 to LEE5), with the LEE5 operon encoding T3SS effectors involved in the intimate adherence of bacteria to enterocytes. The first operon, LEE1, encodes Ler (LEE-encoded regulator), an H-NS (nucleoid structuring protein) paralog that alleviates the LEE H-NS silencing. We observed that the LEE5 and LEE1 promoters present a bimodal expression pattern, depending on environmental stimuli. One key regulator of bimodal LEE1 and LEE5 expression is ler expression, which fluctuates in response to different growth conditions. Under conditions in vitro considered to be equivalent to nonoptimal conditions for virulence, the opposing regulatory effects of H-NS and Ler can lead to the emergence of two bacterial subpopulations. H-NS and Ler share nucleation binding sites in the LEE5 promoter region, but H-NS binding results in local DNA structural modifications distinct from those generated through Ler binding, at least in vitro Thus, we show how two nucleoid-binding proteins can contribute to the epigenetic regulation of bacterial virulence and lead to opposing bacterial fates. This finding implicates for the first time bacterial-chromatin structural proteins in the bimodal regulation of gene expression.IMPORTANCE Gene expression stochasticity is an emerging phenomenon in microbiology. In certain contexts, gene expression stochasticity can shape bacterial epigenetic regulation. In enteropathogenic Escherichia coli (EPEC), the interplay between H-NS (a nucleoid structuring protein) and Ler (an H-NS paralog) is required for bimodal LEE5 and LEE1 expression, leading to the emergence of two bacterial subpopulations (with low and high states of expression). The two proteins share mutual nucleation binding sites in the LEE5 promoter region. In vitro, the binding of H-NS to the LEE5 promoter results in local structural modifications of DNA distinct from those generated through Ler binding. Furthermore, ler expression is a key parameter modulating the variability of the proportions of bacterial subpopulations. Accordingly, modulating the production of Ler into a nonpathogenic E. coli strain reproduces the bimodal expression of LEE5 Finally, this study illustrates how two nucleoid-binding proteins can reshape the epigenetic regulation of bacterial virulence.
    Mots-clés : ACTINO, bacterial chromatin, bet-hedging, bimodal expression, EPEC, H-NS, LEE encoded regulator, Ler, MICROBIO, nongenetic variability, nucleoid-associated protein, Stochasticity, virulence regulation.

  • S. Najah, T. M. Chong, C. Gerbaud, K. - G. Chan, L. Mellouli, et J. - L. Pernodet, « Complete Genome Sequence of Streptomyces sp. TN58, a Producer of Acyl Alpha-l-Rhamnopyranosides », Genome Announcements, vol. 5, nᵒ 34, août 2017.
    Résumé : Streptomyces sp. TN58, isolated from a Tunisian soil sample, produces several natural products, including acyl alpha-l-rhamnopyranosides. It possesses a 7.6-Mb linear chromosome. This is, to our knowledge, the first genome sequence of a microorganism known to produce acyl alpha-l-rhamnopyranosides, and it will be helpful to study the biosynthesis of these specialized metabolites.
    Mots-clés : ACTINO, MICROBIO.


  • A. Kish, J. - C. Gaillard, J. Armengaud, et C. Elie, « Post-translational methylations of the archaeal Mre11:Rad50 complex throughout the DNA damage response », Molecular Microbiology, vol. 100, nᵒ 2, p. 362-378, avr. 2016.
    Résumé : The Mre11:Rad50 complex is central to DNA double strand break repair in the Archaea and Eukarya, and acts through mechanical and nuclease activities regulated by conformational changes induced by ATP binding and hydrolysis. Despite the widespread use of Mre11 and Rad50 from hyperthermophilic archaea for structural studies, little is known in the regulation of these proteins in the Archaea. Using purification and mass spectrometry approaches allowing nearly full sequence coverage of both proteins from the species Sulfolobus acidocaldarius, we show for the first time post-translational methylation of the archaeal Mre11:Rad50 complex. Under basal growth conditions, extensive lysine methylations were identified in Mre11 and Rad50 dynamic domains, as well as methylation of a few aspartates and glutamates, including a key Mre11 aspartate involved in nuclease activity. Upon γ-irradiation induced DNA damage, additional methylated residues were identified in Rad50, notably methylation of Walker B aspartate and glutamate residues involved in ATP hydrolysis. These findings strongly suggest a key role for post-translational methylation in the regulation of the archaeal Mre11:Rad50 complex and in the DNA damage response.
    Mots-clés : ACTINO, Adenosine Triphosphate, Archaea, Archaeal Proteins, DNA, DNA Breaks, Double-Stranded, DNA Damage, DNA Repair, DNA-Binding Proteins, Endodeoxyribonucleases, Exodeoxyribonucleases, Methylation, MICROBIO, Protein Binding, Protein Processing, Post-Translational, Sulfolobus acidocaldarius.


  • H. Boubakri, N. Seghezzi, M. Duchateau, M. Gominet, O. Kofroňová, O. Benada, P. Mazodier, et J. - L. Pernodet, « The Absence of Pupylation (Prokaryotic Ubiquitin-Like Protein Modification) Affects Morphological and Physiological Differentiation in Streptomyces coelicolor », Journal of Bacteriology, vol. 197, nᵒ 21, p. 3388-3399, nov. 2015.
    Résumé : Protein turnover is essential in all living organisms for the maintenance of normal cell physiology. In eukaryotes, most cellular protein turnover involves the ubiquitin-proteasome pathway, in which proteins tagged with ubiquitin are targeted to the proteasome for degradation. In contrast, most bacteria lack a proteasome but harbor proteases for protein turnover. However, some actinobacteria, such as mycobacteria, possess a proteasome in addition to these proteases. A prokaryotic ubiquitination-like tagging process in mycobacteria was described and was named pupylation: proteins are tagged with Pup (prokaryotic ubiquitin-like protein) and directed to the proteasome for degradation. We report pupylation in another actinobacterium, Streptomyces coelicolor. Both the morphology and life cycle of Streptomyces species are complex (formation of a substrate and aerial mycelium followed by sporulation), and these bacteria are prolific producers of secondary metabolites with important medicinal and agricultural applications. The genes encoding the pupylation system in S. coelicolor are expressed at various stages of development. We demonstrated that pupylation targets numerous proteins and identified 20 of them. Furthermore, we established that abolition of pupylation has substantial effects on morphological and metabolic differentiation and on resistance to oxidative stress. In contrast, in most cases, a proteasome-deficient mutant showed only modest perturbations under the same conditions. Thus, the phenotype of the pup mutant does not appear to be due solely to defective proteasomal degradation. Presumably, pupylation has roles in addition to directing proteins to the proteasome. IMPORTANCE: Streptomyces spp. are filamentous and sporulating actinobacteria, remarkable for their morphological and metabolic differentiation. They produce numerous bioactive compounds, including antifungal, antibiotic, and antitumor compounds. There is therefore considerable interest in understanding the mechanisms by which Streptomyces species regulate their complex physiology and production of bioactive compounds. We studied the role in Streptomyces of pupylation, a posttranslational modification that tags proteins that are then directed to the proteasome for degradation. We demonstrated that the absence of pupylation had large effects on morphological differentiation, antibiotic production, and resistance to oxidative stress in S. coelicolor. The phenotypes of pupylation and proteasome-defective mutants differed and suggest that pupylation acts in a proteasome-independent manner in addition to its role in proteasomal degradation.
    Mots-clés : ACTINO, Amino Acid Sequence, Bacterial Proteins, Gene Deletion, MICROBIO, Molecular Sequence Data, Protein Processing, Post-Translational, Sequence Alignment, Streptomyces coelicolor.

  • I. B. Jacques, M. Moutiez, J. Witwinowski, E. Darbon, C. Martel, J. Seguin, E. Favry, R. Thai, A. Lecoq, S. Dubois, J. - L. Pernodet, M. Gondry, et P. Belin, « Analysis of 51 cyclodipeptide synthases reveals the basis for substrate specificity », Nature Chemical Biology, vol. 11, nᵒ 9, p. 721-727, sept. 2015.
    Résumé : Cyclodipeptide synthases (CDPSs) constitute a family of peptide bond-forming enzymes that use aminoacyl-tRNAs for the synthesis of cyclodipeptides. Here, we describe the activity of 41 new CDPSs. We also show that CDPSs can be classified into two main phylogenetically distinct subfamilies characterized by specific functional subsequence signatures, named NYH and XYP. All 11 previously characterized CDPSs belong to the NYH subfamily, suggesting that further special features may be yet to be discovered in the other subfamily. CDPSs synthesize a large diversity of cyclodipeptides made up of 17 proteinogenic amino acids. The identification of several CDPSs having the same specificity led us to determine specificity sequence motifs that, in combination with the phylogenetic distribution of CDPSs, provide a first step toward being able to predict the cyclodipeptides synthesized by newly discovered CDPSs. The determination of the activity of ten more CDPSs with predicted functions constitutes a first experimental validation of this predictive approach.
    Mots-clés : ACTINO, Amino Acid Motifs, Bacterial Proteins, BIOCELL, BIOSYN, Computational Biology, Cyclization, Databases, Genetic, Dipeptides, Escherichia coli, Fungal Proteins, gene expression, MICROBIO, Molecular Sequence Data, Peptide Biosynthesis, Nucleic Acid-Independent, Peptide Synthases, Peptides, Cyclic, Phylogeny, Protein Structure, Tertiary, Recombinant Proteins, RNA, Transfer, Amino Acyl, Substrate Specificity.

  • Y. Li, R. Ducasse, S. Zirah, A. Blond, C. Goulard, E. Lescop, C. Giraud, A. Hartke, E. Guittet, J. - L. Pernodet, et S. Rebuffat, « Characterization of Sviceucin from Streptomyces Provides Insight into Enzyme Exchangeability and Disulfide Bond Formation in Lasso Peptides », ACS chemical biology, vol. 10, nᵒ 11, p. 2641-2649, nov. 2015.
    Résumé : Lasso peptides are bacterial ribosomally synthesized and post-translationally modified peptides. They have sparked increasing interest in peptide-based drug development because of their compact, interlocked structure, which offers superior stability and protein-binding capacity. Disulfide bond-containing lasso peptides are rare and exhibit highly sought-after activities. In an effort to expand the repertoire of such molecules, we heterologously expressed, in Streptomyces coelicolor, the gene cluster encoding sviceucin, a type I lasso peptide with two disulfide bridges originating from Streptomyces sviceus, which allowed it to be fully characterized. Sviceucin and its reduced forms were characterized by mass spectrometry and peptidase digestion. The three-dimensional structure of sviceucin was determined using NMR. Sviceucin displayed antimicrobial activity selectively against Gram-positive bacteria and inhibition of fsr quorum sensing in Enterococcus faecalis. This study adds sviceucin to the type I lasso peptide family as a new representative. Moreover, new clusters encoding disulfide-bond containing lasso peptides from Actinobacteria were identified by genome mining. Genetic and functional analyses revealed that the formation of disulfide bonds in sviceucin does not require a pathway-encoded thiol-disulfide oxidoreductase. Most importantly, we demonstrated the functional exchangeability of the sviceucin and microcin J25 (a non-disulfide-bridged lasso peptide) macrolactam synthetases in vitro, highlighting the potential of hybrid lasso synthetases in lasso peptide engineering.
    Mots-clés : ACTINO, Amino Acid Sequence, Bacterial Proteins, Chromatography, High Pressure Liquid, Disulfides, Magnetic Resonance Spectroscopy, MICROBIO, Models, Molecular, Molecular Sequence Data, Multigene Family, Peptides, Sequence Alignment, Streptomyces.

  • M. H. Medema, R. Kottmann, P. Yilmaz, M. Cummings, J. B. Biggins, K. Blin, I. de Bruijn, Y. H. Chooi, J. Claesen, R. C. Coates, P. Cruz-Morales, S. Duddela, S. Düsterhus, D. J. Edwards, D. P. Fewer, N. Garg, C. Geiger, J. P. Gomez-Escribano, A. Greule, M. Hadjithomas, A. S. Haines, E. J. N. Helfrich, M. L. Hillwig, K. Ishida, A. C. Jones, C. S. Jones, K. Jungmann, C. Kegler, H. U. Kim, P. Kötter, D. Krug, J. Masschelein, A. V. Melnik, S. M. Mantovani, E. A. Monroe, M. Moore, N. Moss, H. - W. Nützmann, G. Pan, A. Pati, D. Petras, F. J. Reen, F. Rosconi, Z. Rui, Z. Tian, N. J. Tobias, Y. Tsunematsu, P. Wiemann, E. Wyckoff, X. Yan, G. Yim, F. Yu, Y. Xie, B. Aigle, A. K. Apel, C. J. Balibar, E. P. Balskus, F. Barona-Gómez, A. Bechthold, H. B. Bode, R. Borriss, S. F. Brady, A. A. Brakhage, P. Caffrey, Y. - Q. Cheng, J. Clardy, R. J. Cox, R. De Mot, S. Donadio, M. S. Donia, W. A. van der Donk, P. C. Dorrestein, S. Doyle, A. J. M. Driessen, M. Ehling-Schulz, K. - D. Entian, M. A. Fischbach, L. Gerwick, W. H. Gerwick, H. Gross, B. Gust, C. Hertweck, M. Höfte, S. E. Jensen, J. Ju, L. Katz, L. Kaysser, J. L. Klassen, N. P. Keller, J. Kormanec, O. P. Kuipers, T. Kuzuyama, N. C. Kyrpides, H. - J. Kwon, S. Lautru, R. Lavigne, C. Y. Lee, B. Linquan, X. Liu, W. Liu, A. Luzhetskyy, T. Mahmud, Y. Mast, C. Méndez, M. Metsä-Ketelä, J. Micklefield, D. A. Mitchell, B. S. Moore, L. M. Moreira, R. Müller, B. A. Neilan, M. Nett, J. Nielsen, F. O'Gara, H. Oikawa, A. Osbourn, M. S. Osburne, B. Ostash, S. M. Payne, J. - L. Pernodet, M. Petricek, J. Piel, O. Ploux, J. M. Raaijmakers, J. A. Salas, E. K. Schmitt, B. Scott, R. F. Seipke, B. Shen, D. H. Sherman, K. Sivonen, M. J. Smanski, M. Sosio, E. Stegmann, R. D. Süssmuth, K. Tahlan, C. M. Thomas, Y. Tang, A. W. Truman, M. Viaud, J. D. Walton, C. T. Walsh, T. Weber, G. P. van Wezel, B. Wilkinson, J. M. Willey, W. Wohlleben, G. D. Wright, N. Ziemert, C. Zhang, S. B. Zotchev, R. Breitling, E. Takano, et F. O. Glöckner, « Minimum Information about a Biosynthetic Gene cluster », Nature Chemical Biology, vol. 11, nᵒ 9, p. 625-631, sept. 2015.
    Mots-clés : ACTINO, Alkaloids, bacteria, Computational Biology, Databases, Genetic, Fungi, Genetic Markers, International Cooperation, Metagenome, MICROBIO, Multigene Family, Peptide Biosynthesis, Nucleic Acid-Independent, Peptides, plants, Polyketides, Polysaccharides, Protein Biosynthesis, Terminology as Topic, Terpenes.

  • A. Thibessard, D. Haas, C. Gerbaud, B. Aigle, S. Lautru, J. - L. Pernodet, et P. Leblond, « Complete genome sequence of Streptomyces ambofaciens ATCC 23877, the spiramycin producer », Journal of Biotechnology, vol. 214, p. 117-118, nov. 2015.
    Résumé : Streptomyces ambofaciens ATCC23877 is a soil bacterium industrially exploited for the production of the macrolide spiramycin which is used in human medicine as an antibacterial and anti-toxoplasmosis chemical. Its genome consists of a 8.3 Mbp linear chromosome and a 89 kb circular plasmid. The complete genome sequence reported here will enable us to investigate Streptomyces genome evolution and to discover new secondary metabolites with potential applications notably in human medicine.
    Mots-clés : ACTINO, Chromosomes, Bacterial, Evolution, Molecular, Gene clusters, Genome instability, Genome sequence, Genome, Bacterial, MICROBIO, Plasmids, Soil Microbiology, Spiramycin, Streptomyces, Streptomyces ambofaciens.

  • A. Vingadassalon, F. Lorieux, M. Juguet, G. Le Goff, C. Gerbaud, J. - L. Pernodet, et S. Lautru, « Natural combinatorial biosynthesis involving two clusters for the synthesis of three pyrrolamides in Streptomyces netropsis », ACS chemical biology, vol. 10, nᵒ 2, p. 601-610, févr. 2015.
    Résumé : The pyrrolamides constitute a small family of secondary metabolites that are known for their ability to bind noncovalently to the DNA minor groove with some sequence specificity. To date, only a single pyrrolamide biosynthetic gene cluster has been reported, directing the synthesis of congocidine (netropsin) in Streptomyces ambofaciens. In this study, we improve our understanding of pyrrolamide biosynthesis through the identification and characterization of the gene cluster responsible for the production of distamycin in Streptomyces netropsis DSM40846. We discover that the strain produces two other pyrrolamides, the well-characterized congocidine and a congocidine/distamycin hybrid that we named disgocidine. S. netropsis DSM40846 genome analysis led to the identification of two distinct pyrrolamide-like biosynthetic gene clusters. We show here that these two clusters are reciprocally dependent for the production of the three pyrrolamide molecules. Furthermore, based on detailed functional analysis of these clusters, we propose a biosynthetic route to congocidine and distamycin and an updated model for pyrrolamide assembly. The synthesis of disgocidine, the distamycin/congocidine hybrid, appears to constitute the first example of "natural combinatorial biosynthesis" between two related biosynthetic pathways. Finally, we analyze the genomic context of the two biosynthetic gene clusters and suggest that the presently interdependent clusters result from the coevolution of two ancestral independent pyrrolamide gene clusters.
    Mots-clés : ACTINO, Anti-Bacterial Agents, Biological Evolution, Combinatorial Chemistry Techniques, Distamycins, Gene Expression Regulation, Bacterial, MICROBIO, Molecular Structure, Multigene Family, Streptomyces.
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