Institute for Integrative Biology of the Cell (I2BC),
Head of the group “Molecular Microbiology of Actinomycetes”
Head of the Microbiology department
Avenue de la Terrasse
91190 Gif-sur-Yvette Cedex
+33 1 69 82 62 42
The group "Molecular Microbiology of Actinomycetes", headed by Jean-Luc Pernodet, is studying the specialized metabolism of actinobacteria. Natural products biosynthesized by this bacterial phylum are at the origin of numerous drugs used in human medicine, especially as antimicrobials. Moreover, it is clear that the ability of microorganisms to synthesize natural products had been seriously underestimated and that microorganisms represent a promising source for the discovery of new bioactive compounds. As there is an urgent need for new drugs, especially in the anti-infective field, various strategies are being developed to gain access to the hidden specialized metabolome of microorganisms and to increase the chemical diversity of the specialized metabolites that they synthesize. The group participates in these efforts by developing novel approaches for the mining of microbial genomes and by studying the biosynthesis of natural products and its regulation in Actinobacteria. The studies conducted in the group combine bacterial genomics and genetics, microbiology, molecular biology, biochemistry and analytical chemistry to identify novel biosynthetic gene clusters directing the biosynthesis of natural products, to establish biosynthetic pathways and to characterize the compounds biosynthesized. The group was for instance the first to characterize the biosynthetic pathways of antibiotics from the pyrrolamide family (Chem Biol 2009, 16:421-431; Angew Chem Int Ed 2012, 51:7454-7458; ACS Chem Biol 2015 10:601-610) or, in collaboration with the group of M. Gondry, a novel family of tRNA-dependent enzymes catalyzing the formation of diketopiperazines (Nat Chem Biol 2009, 5:414-420, Nat Chem Biol 2015, 11:721-727). Diketopiperazines are a family of bioactive compounds, several of which have antibiotic activity. Therefore, these studies are directly connected with the early stages of antibiotic discovery. The group has a strong expertise in this field of research and is now interested in developing synthetic biology approaches for the biosynthesis of novel bioactive compounds. The group is involved in several projects aiming at exploring and exploiting the diversity of the microbial specialized metabolism, e.g. the project EVOBIOTIC supported by JPIAMR and other projects supported by the French National Agency for Research. It also participates in two national networks, one dealing with antimicrobial peptides and the other with systems and synthetic biology.
The Institute for Integrative Biology of the Cell (I2BC, UMR 9198 CNRS-CEA-Université Paris-Sud, Université Paris-Saclay) is one of the largest French academic institutes in the domain of biological sciences. It is located on the Paris-Saclay campus, a large scientific and technologic cluster situated in the south of Paris. The Institute for Integrative Biology of the Cell comprises 74 research groups organized in five disciplinary departments. Currently, it has about 750 staff members, including 440 permanent employees. Within the institute several technological platforms provide access to state-of-the-art equipment and expertise for sequencing, imaging, biochemical and biophysical characterization of biological compounds.
The Microbiology department is composed of 13 research groups. These groups have a common interest in answering fundamental questions related to the biology of microorganisms at the molecular, cellular and population levels. Three main themes emerge from the research carried out by the different groups in the department: microbial metabolism (including specialized metabolism), microbial envelopes, and the interactions of microbes with their hosts and the environment. The group “Molecular Microbiology of Actinomycetes”, headed by Jean-Luc Pernodet, is exploring and exploiting the specialized metabolism of actinobacteria, characterizing novel natural product biosynthetic gene clusters, the associated pathways and the compounds produced.
The research of other groups from the department is strongly connected with the main theme of the proposed network. The research in the group “Enzymology and non-ribosomal peptide biosynthesis” headed by M. Gondry focuses on non-ribosomal synthesis of peptide natural products, and more particularly, cyclodipeptides and their complex derivatives, diketopiperazines, many of which possess antibiotic activitiy. The group “Energetic Metabolism of Streptomyces” headed by M-J. Virolle is interested in the elucidation of the links between primary metabolism, storage lipid metabolism and antibiotic production in Streptomyces in order to elaborate a systemic understanding of Streptomyces metabolism in condition of antibiotic production. The group “Bacterial cell envelopes and antibiotics” headed by D. Mengin-Lecreulx develops detailed investigations of the metabolism and structure of peptidoglycan, one of the main components of the bacterial cell wall. All the enzymes involved in this process constitute potential targets that could be exploited for a search of new antibiotics. These groups have the required expertise and are eager to join this network in the future.
JL Pernodet and members of his group will provide their expertise in natural product biosynthesis by bacteria and more precisely in molecular microbiology approaches to identify, characterize and engineer biosynthetic gene clusters and pathways. The group has developed specific bioinformatic tools for mining microbial genomes. Genetic tools for synthetic biology approaches in actinobacteria are also being developed in the group. All these tools will be available for all members of the network. The group could also contribute by screening compounds for specific activities such as quorum-quenching, i.e. the perturbation of bacterial quorum-sensing.