Radical SAM enzymes for innovative RiPP biosynthesis – SAM4RiPP

Ribosomally-synthesized and post-translationally modified peptides (RiPPs) are an emerging class of natural products mainly produced by bacteria. These peptides contain myriad post-translational modifications which confer them with a wide structural diversity and major biological properties (e.g. antibiotic and anti-cancer activities).
Among the diverse enzymes that install post-translational modifications in RiPPs, radical SAM enzymes have recently emerged as key biocatalysts. These enzymes, which form one of the largest superfamily of enzymes, catalyze a broad range of chemically complex and often unprecedented biochemical transformations. In the frame of the SAM4RiPP project, we aim to explore the mechanism and biosynthetic potential of novel radical SAM enzymes in order (i) to better understand how these fascinating biocatalysts interact and modify their peptide substrates and (ii) to develop novel hybrid RiPPs with engineered properties.
Indeed, thanks to their biosynthetic logic, RiPPs are very attractive products to develop, based on synthetic biology approaches, innovative antibiotics and to tune the human microbiota.