Direct evidence that the rifamycin polyketide synthase assembles polyketide chains processively

被引:121
作者
Yu, TW
Shen, YM
Doi-Katayama, Y
Tang, L
Park, C
Moore, BS
Hutchinson, CR
Floss, HG
机构
[1] Univ Wisconsin, Sch Pharm, Madison, WI 53706 USA
[2] Univ Wisconsin, Dept Bacteriol, Madison, WI 53706 USA
[3] Univ Washington, Dept Chem, Seattle, WA 98195 USA
关键词
D O I
10.1073/pnas.96.16.9051
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The assembly of the polyketide backbone of rifamycin B on the type I rifamycin polyketide synthase (PKS), encoded by the rifA-rifE genes, is terminated by the product of the rifF gene, an amide synthase that releases the completed undecaketide as its macrocyclic lactam. Inactivation of rifE gives a rifamycin B nonproducing mutant that still accumulates a series of linear polyketides ranging from the tetra- to a decaketide, also detected in the wild type, demonstrating that the PKS operates in a processive manner. Disruptions of the rifD module 8 and rifE module 9 and module 10 genes also result in accumulation of such linear polyketides as a consequence. of premature termination of polyketide assembly. Whereas the tetraketide carries an unmodified aromatic chromophore, the penta- through decaketides have undergone oxidative cyclization to the naphthoquinone, suggesting that this modification occurs during, not after, PKS assembly. The structure of one of the accumulated compounds together with O-18 experiments suggests that this oxidative cyclization produces an 8-hydroxy-7,8-dihydronaphthoquinone structure that, after the stage of proansamycin X, is dehydrogenated to an 8-hydroxynaphthoquinone.
引用
收藏
页码:9051 / 9056
页数:6
相关论文
共 32 条
[1]   BIOSYNTHETIC ORIGINS OF THE OXYGEN-ATOMS IN THE ANSAMYCIN ANTIBIOTICS RIFAMYCIN-B, RIFAMYCIN-O, AND RIFAMYCIN-S [J].
ANDERSON, MG ;
MONYPENNY, D ;
RICKARDS, RW ;
ROTHSCHILD, JM .
JOURNAL OF THE CHEMICAL SOCIETY-CHEMICAL COMMUNICATIONS, 1989, (05) :311-313
[2]   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
[3]   X-RAY ANALYSIS OF STRUCTURE OF RIFAMYCIN B1 [J].
BRUFANI, M ;
FEDELI, W ;
VACIAGO, A ;
GIACOMELLI, G .
EXPERIENTIA, 1964, 20 (06) :339-&
[4]   MACROLIDE BIOSYNTHESIS .4. INTACT INCORPORATION OF A CHAIN-ELONGATION INTERMEDIATE INTO ERYTHROMYCIN [J].
CANE, DE ;
YANG, CC .
JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 1987, 109 (04) :1255-1257
[5]   Biochemistry - Harnessing the biosynthetic code: Combinations, permutations, and mutations [J].
Cane, DE ;
Walsh, CT ;
Khosla, C .
SCIENCE, 1998, 282 (5386) :63-68
[6]   MODULAR ORGANIZATION OF GENES REQUIRED FOR COMPLEX POLYKETIDE BIOSYNTHESIS [J].
DONADIO, S ;
STAVER, MJ ;
MCALPINE, JB ;
SWANSON, SJ ;
KATZ, L .
SCIENCE, 1991, 252 (5006) :675-679
[7]  
GHISALBA O, 1985, CHIMIA, V39, P79
[8]   EARLY INTERMEDIATES IN BIOSYNTHESIS OF ANSAMYCINS .1. ISOLATION AND IDENTIFICATION OF PROTORIFAMYCIN-I [J].
GHISALBA, O ;
TRAXLER, P ;
NUESCH, J .
JOURNAL OF ANTIBIOTICS, 1978, 31 (11) :1124-1131
[9]   A GENETIC APPROACH TO THE BIOSYNTHESIS OF THE RIFAMYCIN-CHROMOPHORE IN NOCARDIA-MEDITERRANEI .3. ISOLATION AND IDENTIFICATION OF AN EARLY AROMATIC ANSAMYCIN-PRECURSOR CONTAINING THE 7-CARBON AMINO STARTER-UNIT AND 3 INITIAL ACETATE-PROPIONATE-UNITS OF THE ANSA CHAIN [J].
GHISALBA, O ;
FUHRER, H ;
RICHTER, WJ ;
MOSS, S .
JOURNAL OF ANTIBIOTICS, 1981, 34 (01) :58-63
[10]   ENGINEERING HYBRID GENES WITHOUT THE USE OF RESTRICTION ENZYMES - GENE-SPLICING BY OVERLAP EXTENSION [J].
HORTON, RM ;
HUNT, HD ;
HO, SN ;
PULLEN, JK ;
PEASE, LR .
GENE, 1989, 77 (01) :61-68