The hedamycin locus implicates a novel aromatic PKS priming mechanism

被引：78

作者：

Bililign, T

Hyun, CG

Williams, JS

Czisny, AM

Thorson, JS

机构：

[1] Univ Wisconsin, Sch Pharm, Lab Biosynthet Chem, Pharmaceut Sci Div, Madison, WI 53705 USA

[2] Cornell Univ, Weill Grad Sch Med Sci, Sloan Kettering Div, Mol Pharmacol & Therapeut Program, New York, NY 10021 USA

来源：

CHEMISTRY & BIOLOGY | 2004年 / 11卷 / 07期

关键词：

D O I：

10.1016/j.chembiol.2004.04.016

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

The biosynthetic gene cluster for the pluramycin-type antitumor antibiotic hedamycin has been cloned from Streptomyces griseoruber. Sequence analysis of the 45.6 kb region revealed a variety of unique features such as a fabH homolog (KSIII), an acyltransferase (AT) gene, a set of type I polyketide synthase (PKS) genes, and two putative C-glycosyltransferase genes. As the first report of the cloning of the biosynthetic gene cluster for the pluramycin antibiotics, this work suggests that the biosynthesis of pluramycins utilize an iterative type I PKS system for the generation of a novel starter unit that subsequently primes the type II PKS system. It also implicates the involvement of a second catalytic ketosynthase (KSIII) to regulate this unusual priming step. Gene disruption is used to confirm the importance of both type I and II PKS genes for the biosynthesis of hedamycin.

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页码：959 / 969

页数：11

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