Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG

Shogo Mori, Dinesh Simkhada, Huitu Zhang, Megan S. Erb, Yang Zhang, Howard Williams, Dmytro Fedoseyenko, William Russell, Doyong Kim, Nathan Fleer, Steven E. Ealick, Coran M H Watanabe

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4 Scopus citations

Abstract

The azinomycins are a family of potent antitumor agents with the ability to form interstrand cross-links with DNA. This study reports on the unusual biosynthetic formation of the 5-methyl naphthoate moiety, which is essential for effective DNA association. While sequence analysis predicts that the polyketide synthase (AziB) catalyzes the formation of this naphthoate, 2-methylbenzoic acid, a truncated single-ring product, is formed instead. We demonstrate that the thioesterase (AziG) acts as a chain elongation and cyclization (CEC) domain and is required for the additional two rounds of chain extension to form the expected product.

Original languageEnglish (US)
Pages (from-to)704-714
Number of pages11
JournalBiochemistry
Volume55
Issue number4
DOIs
StatePublished - Feb 2 2016
Externally publishedYes

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ASJC Scopus subject areas

  • Biochemistry

Cite this

Mori, S., Simkhada, D., Zhang, H., Erb, M. S., Zhang, Y., Williams, H., Fedoseyenko, D., Russell, W., Kim, D., Fleer, N., Ealick, S. E., & Watanabe, C. M. H. (2016). Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG. Biochemistry, 55(4), 704-714. https://doi.org/10.1021/acs.biochem.5b01050