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Published on: October 4, 2019
Biosynthesis of the enediyne antitumor antibiotic C-1027
Wen Liu1, Steven D Christenson, Scott Standage
1Division of Pharmaceutical Sciences, University of Wisconsin, Madison, WI 53705, USA.
Abstract:
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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