Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis

Chem Biol. 2008 Jul 21;15(7):693-705. doi: 10.1016/j.chembiol.2008.05.021.


Azinomycin B is a complex natural product containing densely assembled functionalities with potent antitumor activity. Cloning and sequence analysis of the azi gene cluster revealed an iterative type I polyketide synthase (PKS) gene, five nonribosomal peptide synthetases (NRPSs) genes and numerous genes encoding the biosynthesis of unusual building blocks and tailoring steps for azinomycin B production. Characterization of AziB as a 5-methyl-naphthoic acid (NPA) synthase showed a distinct selective reduction pattern in aromatic polyketide biosynthesis governed by bacterial iterative type I PKSs. Heterologous expression established the PKS-post modification route from 5-methyl-NPA to reach the first building block 3-methoxy-5-methyl-NPA. This proposed azinomycin B biosynthetic pathway sets the stage to investigate the enzymatic mechanisms for building structurally unique and pharmaceutically important groups, including the unprecedented azabicyclic ring system and highly active epoxide moiety.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / chemistry
  • Carboxylic Acids / chemistry
  • Carboxylic Acids / metabolism*
  • Chemistry, Pharmaceutical / methods
  • Gene Library
  • Genes, Bacterial
  • Genome
  • Intercellular Signaling Peptides and Proteins
  • Models, Chemical
  • Models, Genetic
  • Molecular Conformation
  • Multienzyme Complexes / chemistry
  • Multigene Family
  • Naphthalenes / chemistry
  • Naphthalenes / metabolism*
  • Peptides / chemistry*
  • Plasmids / metabolism
  • Polyketide Synthases / chemistry*
  • Polyketide Synthases / genetics
  • Streptomyces / metabolism*


  • Amino Acids
  • Carboxylic Acids
  • Intercellular Signaling Peptides and Proteins
  • Multienzyme Complexes
  • Naphthalenes
  • Peptides
  • azinomycin B
  • 1-naphthoic acid
  • Polyketide Synthases