Consequences of Conformational Preorganization in Sesquiterpene Biosynthesis: Theoretical Studies on the Formation of the Bisabolene, Curcumene, Acoradiene, Zizaene, Cedrene, Duprezianene, and Sesquithuriferol Sesquiterpenes
Consequences of Conformational Preorganization in Sesquiterpene Biosynthesis: Theoretical Studies on the Formation of the Bisabolene, Curcumene, Acoradiene, Zizaene, Cedrene, Duprezianene, and Sesquithuriferol Sesquiterpenes
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DOI：
10.1021/ja9005332
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发表时间：
2009-06-17
影响因子：
15
通讯作者：
Tantillo, Dean J.
中科院分区：
文献类型：
--
作者：
Hong, Young J.;Tantillo, Dean J.
几个倍半萜家族的环化机制的量子化学计算提出是密切相关的，在生物意义上（红没药烯，姜黄烯，acoradiene，zizaene（zizaene，isozizaene，epi-zizaene，epi-isozaene），雪松烯（α/β-雪松烯和7-epi-alpha/β-雪松烯），duprezianene，和sesquithuriferol家族）进行了描述。这些计算的结果的基础上，我们建议，可在酶活性位点的红没药基阳离子的构象是形成的倍半萜的结构和相对立体化学的主要决定因素。我们还建议，为了形成zizaene和epi-cedrene，红没药基阳离子的初始形成的构象的大量构象变化是必要的。鉴于红没药基阳离子的生产构象不一定反映在相应的酶活性位点结合法呢基二磷酸的原始方向，我们得出结论，单独的法呢基二磷酸的折叠并不总是决定环化产物的结构和相对立体化学。此外，动态匹配在确定产品分布和酶促形成的二级碳正离子的潜在作用进行了讨论。
Quantum chemical calculations on cyclization mechanisms for several sesquiterpene families proposed to be closely related to each other in a biogenic sense (the bisabolene, curcumene, acoradiene, zizaene (zizaene, isozizaene, epi-zizaene, and epi-isozizaene), cedrene (alpha/beta-cedrenes and 7-epi-alpha/beta-cedrenes), duprezianene, and sesquithuriferol families) are described. On the basis of the results of these calculations, we suggest that the conformation of the bisabolyl cation attainable in an enzyme active site is a primary determinant of the structure and relative stereochemistry of the sesquiterpenes formed. We also suggest that substantial conformational changes of initially formed conformers of the bisabolyl cation are necessary in order to form zizaene and epi-cedrene. Given that the productive conformation of the bisabolyl cation does not necessarily reflect the original orientation of farnesyl diphosphate bound in the corresponding enzyme active site, we conclude that folding of farnesyl diphosphate alone does not always dictate the structure and relative stereochemistry of cyclization products. In addition, the potential roles of dynamic matching in determining product distributions and enzyme-promoted formation of secondary carbocations are discussed.