Mechanisms of β-amino acid incorporation in polyketide macrolactam biosynthesis

Macrolactam antibiotics are an important class of macrocyclic polyketides. In recent years, the number of identified β-amino acid-containing macrolactams and their biosynthetic gene clusters have greatly expanded. Functional analyses of vicenistatin biosynthetic enzymes have revealed conserved biosynthetic machinery that incorporates a β-amino acid starter unit into the polyketide skeleton. A VinN-type adenylation enzyme recognizes a specific β-amino acid starter unit and ligates it with a standalone acyl carrier protein (ACP). The resulting β-aminoacyl-ACP is further aminoacylated to yield dipeptidyl-ACP, whose terminal aminoacyl moiety is a characteristic feature of polyketide biosynthetic intermediates. Structural and mechanistic analyses of enzymes that selectively recognize β-amino acids and dipeptide moieties of polyketide intermediates are reviewed.