Structural highlights
Publication Abstract from PubMed
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.
Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG.,Mori S, Simkhada D, Zhang H, Erb MS, Zhang Y, Williams H, Fedoseyenko D, Russell WK, Kim D, Fleer N, Ealick SE, Watanabe CM Biochemistry. 2016 Feb 2;55(4):704-14. doi: 10.1021/acs.biochem.5b01050. Epub, 2016 Jan 19. PMID:26731610[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Mori S, Simkhada D, Zhang H, Erb MS, Zhang Y, Williams H, Fedoseyenko D, Russell WK, Kim D, Fleer N, Ealick SE, Watanabe CM. Polyketide Ring Expansion Mediated by a Thioesterase, Chain Elongation and Cyclization Domain, in Azinomycin Biosynthesis: Characterization of AziB and AziG. Biochemistry. 2016 Feb 2;55(4):704-14. doi: 10.1021/acs.biochem.5b01050. Epub, 2016 Jan 19. PMID:26731610 doi:https://dx.doi.org/10.1021/acs.biochem.5b01050
