埃坡霉素生物合成基因在黄色黏球菌中的异源表达。
Heterologous expression of epothilone biosynthetic genes in Myxococcus xanthus.
作者信息
Julien Bryan, Shah Sanjay
机构信息
Kosan Biosciences, Inc., Hayward, California 94545, USA.
出版信息
Antimicrob Agents Chemother. 2002 Sep;46(9):2772-8. doi: 10.1128/AAC.46.9.2772-2778.2002.
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.
摘要
埃坡霉素是一类潜在的抗癌药物，其稳定微管的方式与紫杉醇（泰素）相似。埃坡霉素由粘细菌纤维堆囊菌产生，该菌的倍增时间为16小时，仅能产生每升毫克量的埃坡霉素A和埃坡霉素B。此外，对纤维堆囊菌进行基因操作很困难。为了在遗传上更易操作且生长更快的宿主中生产埃坡霉素，我们选择了亲缘关系密切且特征最明确的粘细菌黄色粘球菌。我们通过一系列同源重组事件，将包含整个埃坡霉素基因簇的65.4 kb纤维堆囊菌DNA插入到黄色粘球菌的染色体中。所得菌株产生了埃坡霉素A和B。构建一株在P450环氧化酶epoK中含有突变的菌株，导致了埃坡霉素C和D的产生。
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