Steve Ealick's Research Group
Mori S, Simkhada D, Zhang H, Erb MS, Zhang Y, Williams HJ, Fedoseyenko D, Russell WK, Kim D, Fleer N, Ealick SE, and Watanabe CM. Polyketide Ring Expansion Mediated by a Thioesterase, CEC Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG. Biochemistry 55:704-714 (2016).
The azinomycins are a family of potent anti-tumor agents with the ability to form interstrand crosslinks 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.
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