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
Biochemistryjournal_title
Biochemistryauthors
Mori S,Simkhada D,Zhang H,Erb MS,Zhang Y,Williams H,Fedoseyenko D,Russell WK,Kim D,Fleer N,Ealick SE,Watanabe CMdoi
10.1021/acs.biochem.5b01050subject
Has Abstractpub_date
2016-02-02 00:00:00pages
704-14issue
4eissn
0006-2960issn
1520-4995journal_volume
55pub_type
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