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

Research output: Contribution to journalArticle

4 Citations (Scopus)

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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Polyketides
Cyclization
Biosynthesis
Elongation
Polyketide Synthases
DNA
Antineoplastic Agents
Sequence Analysis
Association reactions
2-toluic acid

ASJC Scopus subject areas

  • Biochemistry

Cite this

Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis : Characterization of AziB and AziG. / Mori, Shogo; Simkhada, Dinesh; Zhang, Huitu; Erb, Megan S.; Zhang, Yang; Williams, Howard; Fedoseyenko, Dmytro; Russell, William; Kim, Doyong; Fleer, Nathan; Ealick, Steven E.; Watanabe, Coran M H.

In: Biochemistry, Vol. 55, No. 4, 02.02.2016, p. 704-714.

Research output: Contribution to journalArticle

Mori, S, Simkhada, D, Zhang, H, Erb, MS, Zhang, Y, Williams, H, Fedoseyenko, D, Russell, W, Kim, D, Fleer, N, Ealick, SE & Watanabe, CMH 2016, 'Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG', Biochemistry, vol. 55, no. 4, pp. 704-714. https://doi.org/10.1021/acs.biochem.5b01050
Mori, Shogo ; Simkhada, Dinesh ; Zhang, Huitu ; Erb, Megan S. ; Zhang, Yang ; Williams, Howard ; Fedoseyenko, Dmytro ; Russell, William ; Kim, Doyong ; Fleer, Nathan ; Ealick, Steven E. ; Watanabe, Coran M H. / Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis : Characterization of AziB and AziG. In: Biochemistry. 2016 ; Vol. 55, No. 4. pp. 704-714.
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