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

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.

journal_name

Biochemistry

journal_title

Biochemistry

authors

Mori S,Simkhada D,Zhang H,Erb MS,Zhang Y,Williams H,Fedoseyenko D,Russell WK,Kim D,Fleer N,Ealick SE,Watanabe CM

doi

10.1021/acs.biochem.5b01050

subject

Has Abstract

pub_date

2016-02-02 00:00:00

pages

704-14

issue

4

eissn

0006-2960

issn

1520-4995

journal_volume

55

pub_type

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