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.
Publication types
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aminoglycosides*
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Anti-Bacterial Agents / biosynthesis*
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Antibiotics, Antineoplastic / biosynthesis*
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Chromatography, High Pressure Liquid
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Cloning, Molecular
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Enediynes
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Genes, Bacterial*
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Multienzyme Complexes / chemistry
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Multienzyme Complexes / genetics
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Multienzyme Complexes / metabolism
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Multigene Family
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Mutation
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Open Reading Frames
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Protein Structure, Tertiary
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Streptomyces / enzymology
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Streptomyces / genetics*
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Streptomyces / metabolism*
Substances
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Aminoglycosides
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Anti-Bacterial Agents
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Antibiotics, Antineoplastic
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Enediynes
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Multienzyme Complexes
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C 1027