Cloning and heterologous expression of the epothilone gene cluster
Cloning and heterologous expression of the epothilone gene cluster
复制标题
DOI：
10.1126/science.287.5453.640
复制
发表时间：
2000-01-28
期刊：
影响因子：
56.9
通讯作者：
Julien, B
中科院分区：
文献类型：
--
作者：
Tang, L;Shah, S;Julien, B
聚酮环氧丙酮是一种潜在的抗癌剂，其稳定微管的方式与紫杉醇类似。克隆并测序了纤维粘杆菌中负责伊波硫酮生物合成的基因簇。它编码6个多功能蛋白，包括一个负载模块、一个非核糖体多肽合成酶模块、八个聚酮合成酶模块和一个将脱氧泊硫酮转化为环氧丙硫酮的P450环氧酶。这些基因在天蓝色链霉菌中的同时表达预示着这种重要因子的大量供应。天蓝色链霉菌更容易受到菌株改良，并且生长速度大约是自然生产菌的10倍。
The polyketide epothilone is a potential anticancer agent that stabilizes microtubules in a similar manner to Taxol. The gene cluster responsible for epothilone biosynthesis in the myxobacterium Sorangium cellulosum was cloned and completely sequenced. It encodes six multifunctional proteins composed of a loading module, one nonribosomal peptide synthetase module, eight polyketide synthase modules, and a P450 epoxidase that converts desoxyepothilone into epothilone. Concomitant expression of these genes in the actinomycete Streptomyces coelicolor produced epothilones A and B. Streptomyces coelicolor is more amenable to strain improvement and grows about 10-fold as rapidly as the natural producer, so this heterologous expression system portends a plentiful supply of this important agent.