The leptomycin gene cluster and its heterologous expression in Streptomyces lividans
The leptomycin gene cluster and its heterologous expression in Streptomyces lividans
复制标题
DOI：
10.1038/ja.2005.86
复制
发表时间：
2005-10-01
影响因子：
3.3
通讯作者：
Gramajo, H
中科院分区：
文献类型：
--
作者：
Hu, ZH;Reid, R;Gramajo, H
瘦霉素通过抑制真核细胞核质易位发挥抗真菌和抗肿瘤活性。为了进一步了解来普霉素的生物合成过程，并通过基因工程方法生产来普霉素类似物，从链霉菌ATCC 39366中克隆了一个90 kb的含有来普霉素生物合成簇的DNA片段，并进行了序列测定。lep基因簇由12个聚酮合酶（PKS）模块组成，分布在4个基因（lepA. B、C和D）和P450编码基因。lep基因簇在变铅青链霉菌中的成功表达证实了它的存在，在那里它指导了两种天然同源物-leptomycins A和B的产生。生产来普霉素B表明宿主具有合成乙基丙二酰辅酶A的能力。
Leptomycin exerts its antifungal and anti-tumoral activity via inhibiting nucleo-cytoplasmic translocations in eukaryotic cells. To learn more about the biosynthesis of leptomycin and in an effort to generate leptomycin analogues through genetic engineering, 90 kb segment of DNA containing the putative leptomycin (lep) biosynthesis cluster from Streptomyces sp. ATCC 39366 was cloned and sequenced. The lep cluster consist of 12 polyketide synthase (PKS) modules distributed in four genes (lepA.. B, C and D) and a P450 encoding gene. The lep gene cluster was confirmed by its successful expression in Streptomyces lividans, where it directed the production of the two natural congeners-leptomycins A and B. The production of leptomycin B showed that the host has the capability to synthesize ethylmalonyl-CoA.