Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase-like Enzyme.
Formation of the Δ(18,19) Double Bond and Bis(spiroacetal) in Salinomycin Is Atypically Catalyzed by SlnM, a Methyltransferase-like Enzyme.
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盐霉素中 Delta(18,19) 双键和双（螺缩醛）的形成由类甲基转移酶 SlnM 非典型催化
DOI：
10.1002/anie.201503561
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发表时间：
2015-07-27
期刊：
影响因子：
--
通讯作者：
Bai L
中科院分区：
文献类型：
--
作者：
Jiang C;Qi Z;Kang Q;Liu J;Jiang M;Bai L
盐霉素是一种广泛使用的聚醚类抗球虫药，最近发现具有抗肿瘤活性。然而，其生物合成的机制直到现在仍然主要是推测性的。本文报道的是通过将其活性与Δ 18，19双键和双（螺缩醛）的形成相关联来鉴定与O-甲基转移酶同源的SlnM的前所未有的功能。详细的体内和体外研究显示，使用带正电荷的S-腺苷甲硫氨酸（SAM）或sinefungin作为辅因子的SlnM以高度非典型的方式催化C19的螺环化偶联脱水，以产生盐霉素。
Salinomycin is a widely used polyether coccidiostat and was recently found to have antitumor activities. However, the mechanism of its biosynthesis remained largely speculative until now. Reported herein is the identification of an unprecedented function of SlnM, homologous to O‐methyltransferases, by correlating its activity with the formation of the Δ18,19 double bond and bis(spiroacetal). Detailed in vivo and in vitro investigations revealed that SlnM, using positively charged S‐adenosylmethionine (SAM) or sinefungin as the cofactor, catalyzed the spirocyclization‐coupled dehydration of C19 in a highly atypical fashion to yield salinomycin.