Functional analysis of the aureothin iterative type I polyketide synthase

被引:51
作者
He, J [1 ]
Hertweck, C [1 ]
机构
[1] Hans Knoll Inst Nat Prod Res, D-07745 Jena, Germany
关键词
antibiotics; biosynthesis; natural products; polyketides; streptomyces;
D O I
10.1002/cbic.200400333
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 modular-type polyketide synthase (PKS) that is involved in aureothin (aur) biosynthesis represents one of the first examples in which a single PKS module (AurA) is used in an iterative fashion. Here we report on the heterologous expression of an engineered AurAB fusion protein that unequivocally proves the iterative nature of AurA. In addition, point mutations reveal that aur PKS module 4 participates in polyketide biosynthesis despite its aberrant acyltronsferase domain.
引用
收藏
页码:908 / 912
页数:5
相关论文
共 30 条
[21]   Evidence from engineered gene fusions for the repeated use of a module in a modular polyketide synthase [J].
Olano, C ;
Wilkinson, B ;
Moss, SJ ;
Braña, AF ;
Méndez, C ;
Leadlay, PF ;
Salas, JA .
CHEMICAL COMMUNICATIONS, 2003, (22) :2780-2782
[22]   Cloning, sequencing, and functional analysis of an iterative type I polyketide synthase gene cluster for biosynthesis of the antitumor chlorinated polyenone neocarzilin in "Streptomyces carzinostaticus" [J].
Otsuka, M ;
Ichinose, K ;
Fujii, I ;
Ebizuka, Y .
ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2004, 48 (09) :3468-3476
[23]   A polyketide synthase-peptide synthetase gene cluster from an uncultured bacterial symbiont of Paederus beetles [J].
Piel, J .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2002, 99 (22) :14002-14007
[24]   THE BIOSYNTHETIC GENE-CLUSTER FOR THE POLYKETIDE IMMUNOSUPPRESSANT RAPAMYCIN [J].
SCHWECKE, T ;
APARICIO, JF ;
MOLNAR, I ;
KONIG, A ;
KHAW, LE ;
HAYDOCK, SF ;
OLIYNYK, M ;
CAFFREY, P ;
CORTES, J ;
LESTER, JB ;
BOHM, GA ;
STAUNTON, J ;
LEADLAY, PF .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1995, 92 (17) :7839-7843
[25]   Polyketide biosynthesis: a millennium review [J].
Staunton, J ;
Weissman, KJ .
NATURAL PRODUCT REPORTS, 2001, 18 (04) :380-416
[26]   Skipping in a hybrid polyketide synthase: Evidence for ACP-to-ACP chain transfer [J].
Thomas, I ;
Martin, CJ ;
Wilkinson, CJ ;
Staunton, J ;
Leadlay, PF .
CHEMISTRY & BIOLOGY, 2002, 9 (07) :781-787
[27]  
Walsh CT, 2002, CHEMBIOCHEM, V3, P125
[28]   Novel octaketide macrolides related to 6-deoxyerythronolide B provide evidence for iterative operation of the erythromycin polyketide synthase [J].
Wilkinson, B ;
Foster, G ;
Rudd, BAM ;
Taylor, NL ;
Blackaby, AP ;
Sidebottom, PJ ;
Cooper, DJ ;
Dawson, MJ ;
Buss, AD ;
Gaisser, S ;
Böhm, IU ;
Rowe, CJ ;
Cortés, J ;
Leadlay, PF ;
Staunton, J .
CHEMISTRY & BIOLOGY, 2000, 7 (02) :111-117
[29]   A gene cluster for macrolide antibiotic biosynthesis in Streptomyces venezuelae:: Architecture of metabolic diversity [J].
Xue, YQ ;
Zhao, LS ;
Liu, HW ;
Sherman, DH .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (21) :12111-12116
[30]  
YAMAZAKI M, 1975, CHEM PHARM BULL, V23, P569