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

Publication Type:

Journal Article

Source:

Biochemistry, Volume 55, Issue 4, p.704-14 (2016)

Keywords:

Antineoplastic Agents, Bacterial Proteins, Glycopeptides, Polyketide Synthases, Protein Structure, Tertiary, Streptomyces

Abstract:

<p>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.</p>

PDB: 
5HMB (apo) and 5HMC (5-methyl naphthoic acid complex)
Detector: 
PILATUS
Beamline: 
24-ID-C