Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp DSM4137
Insights into polyether biosynthesis from analysis of the nigericin biosynthetic gene cluster in Streptomyces sp DSM4137
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DOI：
10.1016/j.chembiol.2007.05.011
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发表时间：
2007-06-01
影响因子：
--
通讯作者：
Haydock, Stephen F.
中科院分区：
文献类型：
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作者：
Harvey, Barbara M.;Mironenko, Tatiana;Haydock, Stephen F.
尼日利亚菌素是最早发现的聚醚离子载体之一，但其生物合成仍不清楚。从链霉菌（Streptomyces sp. DSM4137）中偶然克隆出了尼日利亚菌素的生物合成基因簇，该基因簇的缺失使尼日利亚菌素及其密切相关的代谢物阿比利欣的生产中断。尼日利亚菌素生物合成基因与其他聚酮生物合成簇中的对应基因的详细比较促使了对所提出的聚醚生物合成共同途径的重大修订。特别是，我们提供的证据表明，在尼日利亚菌素、南昌霉素和莫能菌素中，一种不寻常的酮合酶样蛋白KSX将最初形成的线性聚酮链转移到一个离散的酰基载体蛋白ACPX上，进行氧化环化。与此一致的是，从莫能菌素基因簇中删除monACPX或monKSX有效地终止了莫能菌素A的生物合成。
Nigericin was among the first polyether ionophores to be discovered, but its biosynthesis remains obscure. The biosynthetic gene cluster for nigericin has been serendipitously cloned from Streptomyces sp. DSM4137, and deletion of this gene cluster abolished the production of both nigericin and the closely related metabolite abierixin. Detailed comparison of the nigericin biosynthetic genes with their counterparts in the biosynthetic clusters for other polyketides has prompted a significant revision of the proposed common pathway for polyether biosynthesis. In particular, we present evidence that in nigericin, nanchangmycin, and monensin, an unusual ketosynthase-like protein, KSX, transfers the initially formed linear polyketide chain to a discrete acyl carrier protein, ACPX, for oxidative cyclization. Consistent with this, deletion of either monACPX or monKSX from the monensin gene cluster effectively abolished monensin A biosynthesis.