Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus

被引:109
作者
Julien, B [1 ]
Shah, S [1 ]
机构
[1] Kosan Biosci Inc, Hayward, CA 94545 USA
关键词
D O I
10.1128/AAC.46.9.2772-2778.2002
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
dEpothilones 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.
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页码:2772 / 2778
页数:7
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