A common mechanism for branching, cyclopropanation, and cyclobutanation reactions in the isoprenoid biosynthetic pathway
A common mechanism for branching, cyclopropanation, and cyclobutanation reactions in the isoprenoid biosynthetic pathway
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DOI：
10.1021/ja0771282
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发表时间：
2008-02-13
影响因子：
15
通讯作者：
Poulter, C. Dale
中科院分区：
文献类型：
--
作者：
Thulasiram, Hirekodathakallu V.;Erickson, Hans K.;Poulter, C. Dale
在自然界中，有四种反应--链延长、环丙烷化、支化和环丁烷化--用于连接类异戊二烯单元以构建超过55000种天然存在的类异戊二烯化合物的碳骨架。通过链延伸产生的那些分子具有头到尾（规则）的碳骨架，而来自环丙烷化、支化或环丁烷化的那些分子具有非头到尾（不规则）的骨架。虽然野生型酶尚未被鉴定用于分支和环丁烷化反应，但是从法呢基二磷酸合酶构建的嵌合蛋白质（链延长）和胆固醇二磷酸合酶（环丙烷化）催化所有四种已知的类异戊二烯偶联反应，得到二磷酸香叶酯的混合物（链延长）、二磷酸胆碱酯（环丙烷化）、二磷酸熏衣草酯（支化）和二磷酸maconelliyl和planococcyl（环丁烷化）。在C1或C2的氢原子或氢原子在二甲基烯丙基二磷酸酯的甲基基团由氘的替代改变了环丙烷化，支化，和环丁烷化产物的分布，通过初级和二级动力学同位素效应上的常见碳阳离子中间体的分配步骤。这些实验建立了中间体形成的顺序，并表明碳阳离子重排和消除步骤的酶介导的控制决定了产物的分布。
Four reactions-chain elongation, cyclopropanation, branching, and cyclobutanation-are used in nature to join isoprenoid units for construction of the carbon skeletons for over 55 000 naturally occurring isoprenoid compounds. Those molecules produced by chain elongation have head-to-tail (regular) carbon skeletons, while those from cyclopropanation, branching, or cyclobutanation have non-head-to-tail (irregular) skeletons. Although wild type enzymes have not been identified for the branching and cyclobutanation reactions, chimeric proteins constructed from farnesyl diphosphate synthase (chain elongation) and chrysanthemyl diphosphate synthase (cyclopropanation) catalyze all four of the known isoprenoid coupling reactions to give a mixture of geranyl diphosphate (chain elongation), chrysanthemyl diphosphate (cyclopropanation), lavandulyl diphosphate (branching), and maconelliyl and planococcyl diphosphate (cyclobutanation). Replacement of the hydrogen atoms at C1 or C2 or hydrogen atoms in the methyl groups of dimethylallyl diphosphate by deuterium alters the distribution of the cyclopropanation, branching, and cyclobutanation products through primary and secondary kinetic isotope effects on the partitioning steps of common carbocationic intermediates. These experiments establish the sequence in which the intermediates are formed and indicate that enzyme-mediated control of the carbocationic rearrangement and elimination steps determines the distribution of products.