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

Abstract

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.

DOI: 10.1016/j.chembiol.2008.05.021
050100200920102011201220132014201520162017
Citations per Year

129 Citations

Semantic Scholar estimates that this publication has 129 citations based on the available data.

See our FAQ for additional information.

Cite this paper

@article{Zhao2008CharacterizationOT, title={Characterization of the azinomycin B biosynthetic gene cluster revealing a different iterative type I polyketide synthase for naphthoate biosynthesis.}, author={Qunfei Zhao and Qingli He and Wei Ding and Mancheng C Tang and Qianjin Kang and Yi Yu and Wei Deng and Qi S. Zhang and Jie Fang and Gongli Tang and Wen Liu}, journal={Chemistry & biology}, year={2008}, volume={15 7}, pages={693-705} }