Affiliation:
1. KOSAN Biosciences, 3832 Bay Center Place, Hayward, CA 94545, USA.
Abstract
The polyketide epothilone is a potential anticancer agent that stabilizes microtubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacterium
Sorangium cellulosum
was cloned and completely sequenced. It encodes six multifunctional proteins composed of a loading module, one nonribosomal peptide synthetase module, eight polyketide synthase modules, and a P450 epoxidase that converts desoxyepothilone into epothilone. Concomitant expression of these genes in the actinomycete
Streptomyces coelicolor
produced epothilones A and B.
Streptomyces coelicolor
is more amenable to strain improvement and grows about 10-fold as rapidly as the natural producer, so this heterologous expression system portends a plentiful supply of this important agent.
Publisher
American Association for the Advancement of Science (AAAS)
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