Mycofactocin biosynthesis: modification of the peptide MftA by the radical S‐adenosylmethionine protein MftC

Mycofactocin is a putative, peptide derived, cofactor that is associated primarily with the Mycobacterium genera including the pathogen M. tuberculosis . The pathway consists of the three genes mftA , mftB , and mftC that encode for the peptide substrate, peptide chaperone, and a radical S‐adenosylmethionine protein ( RS ), respectively. Here, we show that the MftB acts as a peptide chaperone, binding MftA with a submicromolar K D (~ 100 n m ) and MftC with a low micromolar K D (~ 2 μ m ). Moreover, we demonstrate that MftC is a radical S‐adenosylmethionine ( SAM ) enzyme. Finally, we show that MftC catalyzes the oxidative decarboxylation of the peptide MftA.