Biosynthesis of the enediyne antitumor antibiotic C-1027
Biosynthesis of the enediyne antitumor antibiotic C-1027
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DOI：
10.1126/science.1072110
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发表时间：
2002-08-16
期刊：
影响因子：
56.9
通讯作者：
Shen, B
中科院分区：
文献类型：
--
作者：
Liu, W;Christenson, SD;Shen, B
C-1027是一种有效的抗肿瘤药物，具有先前未描述的分子结构和作用方式。对全球链霉菌85千碱基C-1027生物合成基因簇的克隆和表征揭示了(i)一种不同于迄今已知的任何细菌聚酮合成酶的迭代型i型聚酮合成酶，（ii）一种用于9元和10元烯二炔抗生素生物合成的通用聚酮途径，以及（iii）一种来自四个构建块的C-1027发色团的聚合生物合成策略。操纵控制C-1027生物合成的基因使我们能够以预测的方式生产一种烯二炔化合物。
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.