The B-12-Radical SAM enzyme PoyC catalyzes valine C-beta-Methylation during Polytheonamide Biosynthesis

Abstract : Genomic and metagenomic investigations have recently led to the delineation of a novel class of natural products called ribosomally synthesized and post-translationally modified peptides (RiPPs). RiPPs are ubiquitous among living organisms and include pharmaceutically relevant compounds such as antibiotics and toxins. A prominent example is polytheonamide A, which exhibits numerous post-translational modifications, some of which were unknown in ribosomal peptides until recently. Among these post-translational modifications, C-methylations have been proposed to be catalyzed by two putative radical S-adenosylmethionine (rSAM) enzymes, PoyB and PoyC. Here we report the in vitro activity of PoyC, the first B-12-dependent rSAM enzyme catalyzing peptide C-beta-methylation. We show that PoyC catalyzes the formation of S-adenosylhomocysteine and 5'-deoxyadenosine and the transfer of a methyl group to L-valine residue. In addition, we demonstrate for the first time that B-12-rSAM enzymes have a tightly bound MeCbl cofactor that during catalysis transfers a methyl group originating from S-adenosyl-L-methionine. Collectively, our results shed new light on polytheonamide biosynthesis and the large and emerging family of B-12-rSAM enzymes.
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Auberie Parent, Alain Guillot, Alhosna Benjdia, Gwladys Chartier, Jerome Leprince, et al.. The B-12-Radical SAM enzyme PoyC catalyzes valine C-beta-Methylation during Polytheonamide Biosynthesis. Journal of the American Chemical Society, American Chemical Society, 2016, 138 (48), pp.15515-15518. ⟨10.1021/jacs.6b06697⟩. ⟨hal-01605179⟩



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