A transglutaminase homologue as a condensation catalyst in antibiotic assembly lines

A new line in antibioticsAndrimid is a hybrid nonribosomal peptide-polyketide antibiotic that has been isolated from several different types of bacteria in the past twenty years. It is a nanomolar inhibitor of bacterial acetyl-CoA carboxylase, and inhibiting this enzyme blocks a step in prokaryotic fatty acid biosynthesis. Fortin et al. now show that AdmF, one of the enzymes responsible for the biosynthesis of andrimid, is a transglutaminase-like (TGase-like) enzyme that catalyses the formation of a critical amide bond in the natural product. This is the first time a TGase-like enzyme has been shown to be involved in the biosynthesis of an antibiotic. This work suggests that AdmF or related TGase-like enzymes from other microbes may be used to generate new 'unnatural' antibiotics that are active against drug-resistant bacterial pathogens.