Hu Zhihao, Reid Ralph, Gramajo Hugo
Kosan Biosciences Inc, Hayward, CA 94545, USA.
J Antibiot (Tokyo). 2005 Oct;58(10):625-33. doi: 10.1038/ja.2005.86.
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.
细交链孢菌酮酸通过抑制真核细胞中的核质转运发挥其抗真菌和抗肿瘤活性。为了更多地了解细交链孢菌酮酸的生物合成,并努力通过基因工程生成细交链孢菌酮酸类似物,从链霉菌属ATCC 39366中克隆并测序了包含假定的细交链孢菌酮酸(lep)生物合成簇的90 kb DNA片段。lep簇由分布在四个基因(lepA、B、C和D)中的12个聚酮合酶(PKS)模块和一个P450编码基因组成。lep基因簇在变铅青链霉菌中的成功表达证实了这一点,在该菌中它指导了两种天然同系物——细交链孢菌酮酸A和B的产生。细交链孢菌酮酸B的产生表明宿主具有合成乙基丙二酰辅酶A的能力。