Biosynthesis of the enediyne antitumor antibiotic C-1027

被引:250
作者
Liu, W
Christenson, SD
Standage, S
Shen, B [1 ]
机构
[1] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA
[2] Univ Wisconsin, Dept Chem, Madison, WI 53705 USA
[3] Univ Calif Davis, Biochem & Mol Biol Grad Grp, Davis, CA 95616 USA
[4] Univ Calif Davis, Dept Chem, Davis, CA 95616 USA
关键词
D O I
10.1126/science.1072110
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
C-1027 is a potent antitumor agent with a previously undescribed molecular architecture and mode of action. Cloning and characterization of the 85-kilobase C-1027 biosynthesis gene cluster from Streptomyces globisporus revealed (i) an iterative type I polyketide synthase that is distinct from any bacterial polyketide synthases known to date, (ii) a general polyketide pathway for the biosynthesis of both the 9- and 10-membered enediyne antibiotics, and (iii) a convergent biosynthetic strategy for the C-1027 chromophore from four building blocks. Manipulation of genes governing C-1027 biosynthesis allowed us to produce an enediyne compound in a predicted manner.
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收藏
页码:1170 / 1173
页数:5
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