index - Biochimie et Biologie Synthétique

Team ChemSyBio, UMR MICALIS

The human microbiome plays a central role in human physiology. This complex ecosystem is composed of thousands of bacterial species and has a remarkable biosynthetic potential. However, we still have a limited knowledge of its biosynthetic potential and the enzymes that support its functions. In the ChemSyBio team, we have shown that an emerging superfamily of enzymes called "radical SAM enzymes" play a key role in the human microbiome from host colonization to the production of bioactive compounds including antibiotics. These metalloenzymes catalyze chemically challenging reactions using a central radical-based mechanism. Although broadly distributed, the importance of these enzymes has been recently recognized. They are major biocatalysts in the biosynthesis of natural products from small organic compounds to antimicrobial peptides and in the post-translational modification of proteins.

Our laboratory has conducted pioneer studies in the field. By combining a broad range of approaches from biochemistry, analytical chemistry, spectroscopy to structural biology, we have unraveled novel reactions and post-translational modifications catalyzed by radical SAM enzymes, unprecedented mechanisms and protein architectures. Our research aims at obtaining a comprehensive picture of the major enzymes of the microbiome and to develop novel therapeutic strategies targeting the microbiome.

Our research is focused on two main axes:

- RiPP biosynthesis and emerging functions in the microbiome

- Enzyme mechanism and catalytic innovation

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