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Cloning and Heterologous Expression of the Epothilone Gene Cluster
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.
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Cited by
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Staunton, J., & Weissman, K. J. (2001) · Natural Product Reports · doi:10.1039/a909079g · Cited by 1,641
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Weissman, K. J., & Leadlay, P. F. (2005) · Nature Reviews Microbiology · doi:10.1038/nrmicro1287 · Cited by 466
Nonproteinogenic Amino Acid Building Blocks for Nonribosomal Peptide and Hybrid Polyketide Scaffolds
Walsh, C. T., O'Brien, R. V., & Khosla, C. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201208344 · Cited by 406
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Lourie, O. R., Jones, C. R., Bartlett, B. M., Gibbons, P. C., Ruoff, R. S., & Buhro, W. E. (2000) · Chemistry of Materials · doi:10.1021/cm000157q · Cited by 398
Automated genome mining for natural products
Li, M. H., Ung, P. M., Zajkowski, J., Garneau-Tsodikova, S., & Sherman, D. H. (2009) · BMC Bioinformatics · doi:10.1186/1471-2105-10-185 · Cited by 276
Metadata
- Authors
- Tang, L., Shah, S., Chung, L., Carney, J., Katz, L., Khosla, C., & Julien, B.
- Venue
- Science
- Published
- 2000-01-28
- Volume
- 287
- Issue
- 5453
- Pages
- 640-642
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- OpenAlex
- W2036984750
- Cited by
- 424
- References
- 0
- FWCI
- 21.46
- Type
- journal article
- Language
- en
- Open access
- closed
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- Tang, L., Shah, S., Chung, L., Carney, J., Katz, L., Khosla, C., & Julien, B. (2000). Cloning and Heterologous Expression of the Epothilone Gene Cluster. Science. https://doi.org/10.1126/science.287.5453.640
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