Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis
Evidence for the role of the monB genes in polyether ring formation during monensin biosynthesis
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DOI：
10.1016/j.chembiol.2006.01.013
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发表时间：
2006-04-01
影响因子：
--
通讯作者：
Spencer, JB
中科院分区：
文献类型：
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作者：
Gallimore, AR;Stark, CBW;Spencer, JB
离子基聚醚是由线性聚酮精致的立体选择性氧化环化反应产生的，可能是通过三环氧化合物的中间体。我们在这里报道，从莫能菌素生物合成基因簇中删除monBI和monBII基因中的一个或两个，使菌株产生C-3-去甲基莫能菌素和包括C-9-表观莫能菌素A在内的许多次要成分的混合物，代替莫能菌素A和B。所有次要成分通过随后的酸处理有效地转化为莫能菌素。这些数据有力地表明，环氧化物开环和伴随的聚醚环的形成是由MonB酶催化的，而不是像以前认为的那样由MonCII酶催化。与此一致的是，同源模拟表明，Monb型酶的结构与最近从红球红球菌中测定的柠檬烯-1，2-环氧化物水解酶的结构非常相似。
Ionophoric polyethers are produced by the exquisitely stereoselective oxidative cyclization of a linear polyketide, probably via a triepoxide intermediate. We report here that deletion of either or both of the monBI and monBII genes from the monensin biosynthetic gene cluster gave strains that produced, in place of monensins A and B, a mixture of C-3-demethylmonensins and a number of minor components, including C-9-epimonensin A. All the minor components were efficiently converted into monensins by subsequent acid treatment. These data strongly suggest that epoxide ring opening and concomitant polyether ring formation are catalyzed by the MonB enzymes, rather than by the enzyme MonCII as previously thought. Consistent with this, homology modeling shows that the structure of MonB-type enzymes closely resembles the recently determined structure of limonene-1,2-epoxide hydrolase from Rhodococcus erythropolis.