Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120.
Enzymatic synthesis of a bicyclobutane fatty acid by a hemoprotein lipoxygenase fusion protein from the cyanobacterium Anabaena PCC 7120.
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通过来自蓝藻鱼腥藻 PCC 7120 的血红素蛋白脂氧合酶融合蛋白酶促合成双环丁烷脂肪酸。
DOI：
10.1073/pnas.0707148104
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发表时间：
2007
影响因子：
11.1
通讯作者：
Brash,AlanR
中科院分区：
文献类型：
--
作者：
Schneider,Claus;Niisuke,Katrin;Boeglin,WilliamE;Voehler,Markus;Stec,DonaldF;Porter,NedA;Brash,AlanR
多不饱和脂肪酸的生物转化往往导致化学不稳定的产物，如哺乳动物生物学中的前列腺素内源过氧物和白三烯A4环氧化物，以及植物中的丙二烯环氧化物。在这里，我们报告了一种含有高度应变的双环四碳环的脂肪酸的酶法生产，这种部分以前只被认为是化学中机械研究的模型化合物。蓝藻AnabaenaPCC7120的双功能蛋白亚麻酸(C18.3ω3)在脂氧合酶结构域形成9R-羟基过氧基-C18.3ω3，然后由过氧化氢酶相关结构域将9R-氢过氧化氢转化为两个不稳定的烯丙基环氧化物。我们分离鉴定了主要产物为9R，10R-环氧基-11-反式-C18.1，副产物为9R，10R-环氧基-11-反式，13-反式，15顺-C18。ω3为白三烯A型环氧化物。这两种环氧化物的合成可以通过过氧化氢初始转化为环氧烯丙基碳阳离子来理解。重排成中间体双环丁烷离子，然后去质子化得到双环丁烷脂肪酸。这种酶反应在水或有机溶剂中是不可比拟的，在那里会形成开环的环丙烷、环丁烷和高烯丙基产物。鉴于这里显示的高度紧张和不稳定的双环丁烷的酶形成能力，我们的发现表明，在生产高能双环丁烷时，应该研究化学和生物中涉及碳正离子重排的其他转化。
Biological transformations of polyunsaturated fatty acids often lead to chemically unstable products, such as the prostaglandin endoperoxides and leukotriene A4epoxide of mammalian biology and the allene epoxides of plants. Here, we report on the enzymatic production of a fatty acid containing a highly strained bicyclic four-carbon ring, a moiety known previously only as a model compound for mechanistic studies in chemistry. Starting from linolenic acid (C18.3ω3), a dual function protein from the cyanobacteriumAnabaenaPCC 7120 forms 9R-hydroperoxy-C18.3ω3 in a lipoxygenase domain, then a catalase-related domain converts the 9R-hydroperoxide to two unstable allylic epoxides. We isolated and identified the major product as 9R,10R-epoxy-11trans-C18.1 containing a bicyclo[1.1.0]butyl ring on carbons 13–16, and the minor product as 9R,10R-epoxy-11trans,13trans,15cis-C18.ω3, an epoxide of the leukotriene A type. Synthesis of both epoxides can be understood by initial transformation of the hydroperoxide to an epoxy allylic carbocation. Rearrangement to an intermediate bicyclobutonium ion followed by deprotonation gives the bicyclobutane fatty acid. This enzymatic reaction has no parallel in aqueous or organic solvent, where ring-opened cyclopropanes, cyclobutanes, and homoallyl products are formed. Given the capability shown here for enzymatic formation of the highly strained and unstable bicyclobutane, our findings suggest that other transformations involving carbocation rearrangement, in both chemistry and biology, should be examined for the production of the high energy bicyclobutanes.