An ATP-independent strategy for amide bond formation in antibiotic biosynthesis (original) (raw)

A-503083 B, a capuramycin-type antibiotic, is biosynthesized through a novel ATP-independent amide bond formation mechanism. This process involves the S-adenosylmethionine-dependent carboxyl methyltransferase (CapS) and a class C β-lactamase (CapW), which together convert a carboxylic acid into a methyl ester, followed by an ester-amide exchange to form the amide bond. These findings challenge existing paradigms in antibiotic biosynthesis and suggest alternative strategies for carboxylic acid activation.