Details

Autor(en) / Beteiligte

• Parent, Aubérie
• Guillot, Alain
• Benjdia, Alhosna
• Chartier, Gwladys
• Leprince, Jérôme
• Berteau, Olivier

Titel

The B12-Radical SAM Enzyme PoyC Catalyzes Valine Cβ‑Methylation during Polytheonamide Biosynthesis

Ist Teil von

• Journal of the American Chemical Society, 2016-12, Vol.138 (48), p.15515-15518

Ort / Verlag

American Chemical Society

Erscheinungsjahr

2016

Quelle

Alma/SFX Local Collection

Beschreibungen/Notizen

• 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 B12-dependent rSAM enzyme catalyzing peptide Cβ-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 B12-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 B12-rSAM enzymes.