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Science 28 January 2000:
Vol. 287. no. 5453, pp. 640 - 642
DOI: 10.1126/science.287.5453.640
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Reports

Cloning and Heterologous Expression of the Epothilone Gene Cluster

Li Tang, Sanjay Shah, Loleta Chung, John Carney, Leonard Katz, Chaitan Khosla, Bryan Julien *

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.

KOSAN Biosciences, 3832 Bay Center Place, Hayward, CA 94545, USA.
*   To whom correspondence should be addressed. E-mail: julien{at}kosan.com

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Purification, priming, and catalytic acylation of carrier protein domains in the polyketide synthase and nonribosomal peptidyl synthetase modules of the HMWP1 subunit of yersiniabactin synthetase.
Z. Suo, C. C. Tseng, and C. T. Walsh (2000)
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Acyl-CoA hydrolysis by the high molecular weight protein 1 subunit of yersiniabactin synthetase: Mutational evidence for a cascade of four acyl-enzyme intermediates during hydrolytic editing.
Z. Suo, H. Chen, and C. T. Walsh (2000)
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Purification, priming, and catalytic acylation of carrier protein domains in the polyketide synthase and nonribosomal peptidyl synthetase modules of the HMWP1 subunit of yersiniabactin synthetase.
Z. Suo, C. C. Tseng, and C. T. Walsh (2001)
PNAS 98, 99-104
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In vitro reconstitution of the myxochelin biosynthetic machinery of Stigmatella aurantiaca Sg a15: Biochemical characterization of a reductive release mechanism from nonribosomal peptide synthetases.
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PNAS 98, 11136-11141
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Acyl-CoA hydrolysis by the high molecular weight protein 1 subunit of yersiniabactin synthetase: Mutational evidence for a cascade of four acyl-enzyme intermediates during hydrolytic editing.
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Science. ISSN 0036-8075 (print), 1095-9203 (online)