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

来源：

CHEMBIOCHEM | 2005年 / 6卷 / 05期

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.

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收藏

页码：908 / 912

页数：5

相关论文

共 30 条

[1] Biosynthesis of the ansamycin antibiotic rifamycin: deductions from the molecular analysis of the rif biosynthetic gene cluster of Amycolatopsis mediterranei S699 [J].

August, PR ;

Tang, L ;

Yoon, YJ ;

Ning, S ;

Muller, R ;

Yu, TW ;

Taylor, M ;

Hoffmann, D ;

Kim, CG ;

Zhang, XH ;

Hutchinson, CR ;

Floss, HG .

CHEMISTRY & BIOLOGY, 1998, 5 (02) :69-79

[2] The candicidin gene cluster from Streptomyces griseus IMRU 3570 [J].

Campelo, AB ;

Gil, JA .

MICROBIOLOGY-SGM, 2002, 148 :51-59

[3] Biochemistry - Harnessing the biosynthetic code: Combinations, permutations, and mutations [J].

Cane, DE ;

Walsh, CT ;

Khosla, C .

SCIENCE, 1998, 282 (5386) :63-68

[4] Type I polyketide synthase requiring a discrete acyltransferase for polyketide biosynthesis [J].

Cheng, YQ ;

Tang, GL ;

Shen, B .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (06) :3149-3154

[5] AN UNUSUALLY LARGE MULTIFUNCTIONAL POLYPEPTIDE IN THE ERYTHROMYCIN-PRODUCING POLYKETIDE SYNTHASE OF SACCHAROPOLYSPORA-ERYTHRAEA [J].

CORTES, J ;

HAYDOCK, SF ;

ROBERTS, GA ;

BEVITT, DJ ;

LEADLAY, PF .

NATURE, 1990, 348 (6297) :176-178

[6] REPOSITIONING OF A DOMAIN IN A MODULAR POLYKETIDE SYNTHASE TO PROMOTE SPECIFIC CHAIN CLEAVAGE [J].

CORTES, J ;

WIESMANN, KEH ;

ROBERTS, GA ;

BROWN, MJB ;

STAUNTON, J ;

LEADLAY, PF .

SCIENCE, 1995, 268 (5216) :1487-1489

[7] Thioesterases and the premature termination of polyketide chain elongation in rifamycin B biosynthesis by Amycolatopsis mediterranei S699 [J].

Doi-Katayama, Y ;

Yoon, YJ ;

Choi, CY ;

Yu, TW ;

Floss, HG ;

Hutchinson, CR .

JOURNAL OF ANTIBIOTICS, 2000, 53 (05) :484-495

[8] Characterization of the mupirocin biosynthesis gene cluster from Pseudomonas fluorescens NCIMB 10586 [J].

El-Sayed, AK ;

Hothersall, J ;

Cooper, SM ;

Stephens, E ;

Simpson, TJ ;

Thomas, CM .

CHEMISTRY & BIOLOGY, 2003, 10 (05) :419-430

[9] The biosynthesis of the aromatic myxobacterial electron transport inhibitor stigmatellin is directed by a novel type of modular polyketide synthase [J].

Gaitatzis, N ;

Silakowski, B ;

Kunze, B ;

Nordsiek, G ;

Blöcker, H ;

Höfle, G ;

Müller, R .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (15) :13082-13090

[10] New natural epothilones from Sorangium cellulosum, strains So ce90/B2 and So ce90/D13:: Isolation, structure elucidation, and SAR studies [J].

Hardt, IH ;

Steinmetz, H ;

Gerth, K ;

Sasse, F ;

Reichenbach, H ;

Höfle, G .

JOURNAL OF NATURAL PRODUCTS, 2001, 64 (07) :847-856