Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis

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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. © 2008 Elsevier Ltd. All rights reserved.

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Zhao, Q., He, Q., Ding, W., Tang, M., Kang, Q., Yu, Y., … Liu, W. (2008). Characterization of the Azinomycin B Biosynthetic Gene Cluster Revealing a Different Iterative Type I Polyketide Synthase for Naphthoate Biosynthesis. Chemistry and Biology, 15(7), 693–705. https://doi.org/10.1016/j.chembiol.2008.05.021

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