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.
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
Akimasa
A
Miyanaga
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan.
Fumitaka
F
Kudo
Department of Chemistry, Tokyo Institute of Technology, 2-12-1 O-okayama, Meguro-ku, Tokyo 152-8551, Japan. Electronic address: eguchi@chem.titech.ac.jp.
Tadashi
T
Eguchi
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D007769:Lactams / Q000378:metabolism*; D061065:Polyketides / Q000378:metabolism*
D000596:Amino Acids; D007769:Lactams; D061065:Polyketides