Affiliation:
1. Kosan Biosciences, Inc., Hayward, California 94545
Abstract
ABSTRACT
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.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
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