 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 c-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 . 
Supplementary Material