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Biosynthesis of the Enediyne Antitumor Antibiotic C-1027

Science  16 Aug 2002:
Vol. 297, Issue 5584, pp. 1170-1173
DOI: 10.1126/science.1072110

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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.

  • * To whom correspondence should be addressed. E-mail: bshen{at}pharmacy.wisc.edu

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