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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

Bryan Julien* and Sanjay Shah

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.

* Corresponding author. Mailing address: Kosan Biosciences, Inc., 3832 Bay Center Place, Hayward, CA 94545. Phone: (510) 732-8400, ext. 209. Fax: (510) 732-8401. E-mail: julien{at}kosan.com.

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.



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