Different Amide Biosynthesis Route

A newly discovered enzymatic pathway for biosynthesizing amide bonds could prove useful as a means to modify natural products for drug discovery.

Organisms typically make amide bonds via an enzymatic, adenosine triphosphate (ATP) hydrolysis-driven process that converts a carboxylic acid into an acyl-adenylate or acyl-phosphate derivative, followed by substitution of the adenylate or phosphate group with an amine. Now, a study of amide formation in the bacterial biosynthesis of a capuramycin-type antibiotic has revealed an ATP-independent route to amide biosynthesis. The discoverers of the new pathway are Steven G. Van Lanen of the University of Kentucky, Lexington; Koichi Nonaka of Daiichi Sankyo, in Fukushima, Japan; and coworkers (Nat. Chem. Biol., DOI: 10.1038/nchembio.393).

The reaction involves methyl transfer from S-adenosylmethionine, generating S-adenosylhomocysteine and the methyl ester of a carboxylic acid. An ester-amide exchange then converts the methyl ester into an amide.

Sequence analysis of related biosynthetic systems in other microorganisms suggests that this ATP-independent pathway may be widespread in nature, and the findings "now open the door for structural diversification of the capuramycin scaffold using a chemoenzymatic approach," Van Lanen says.