This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Julien, B. Articles by Shah, S. Search for Related Content PubMed PubMed Citation Articles by Julien, B. Articles by Shah, S.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, September 2002, p. 2772-2778, Vol. 46, No. 9
0066-4804/02/$04.00+0     DOI: 10.1128/AAC.46.9.2772-2778.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Heterologous Expression of Epothilone Biosynthetic Genes in Myxococcus xanthus

Kosan Biosciences, Inc., Hayward, California 94545

Received 15 January 2002/ Returned for modification 22 April 2002/ Accepted 1 June 2002

Epothilones are potential anticancer drugs that stabilize microtubules in a manner similar to paclitaxel (Taxol). Epothilones are produced from the myxobacterium Sorangium cellulosum, which has a 16-h doubling time and produces only milligram-per-liter amounts of epothilone A and epothilone B. Furthermore, genetic manipulation of S. cellulosum is difficult. To produce epothilones in a more genetically amenable and rapidly growing host, we chose the closely related and best-characterized myxobacteria Myxococcus xanthus. We inserted 65.4 kb of S. cellulosum DNA that encompassed the entire epothilone gene cluster into the chromosome of M. xanthus by a series of homologous recombination events. The resulting strain produced epothilones A and B. Construction of a strain that contained a mutation in epoK, the P450 epoxidase, resulted in production of epothilones C and D.

This article has been cited by other articles:

• Perlova, O., Fu, J., Kuhlmann, S., Krug, D., Stewart, A. F., Zhang, Y., Muller, R. (2006). Reconstitution of the Myxothiazol Biosynthetic Gene Cluster by Red/ET Recombination and Heterologous Expression in Myxococcus xanthus. Appl. Environ. Microbiol. 72: 7485-7494 [Abstract] [Full Text]  
• Zirkle, R., Ligon, J. M., Molnar, I. (2004). Heterologous production of the antifungal polyketide antibiotic soraphen A of Sorangium cellulosum So ce26 in Streptomyces lividans. Microbiology 150: 2761-2774 [Abstract] [Full Text]  
• Lei, L., Waterman, M. R., Fulco, A. J., Kelly, S. L., Lamb, D. C. (2004). Availability of specific reductases controls the temporal activity of the cytochrome P450 complement of Streptomyces coelicolor A3(2). Proc. Natl. Acad. Sci. USA 101: 494-499 [Abstract] [Full Text]  
• Julien, B. (2003). Characterization of the Integrase Gene and Attachment Site for the Myxococcus xanthus Bacteriophage Mx9. J. Bacteriol. 185: 6325-6330 [Abstract] [Full Text]