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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