Biosynthetic Mechanism of Lanosterol: A Completed Story
Biosynthetic Mechanism of Lanosterol: A Completed Story
复制标题
羊毛甾醇的生物合成机制：一个完整的故事
DOI：
10.1021/acscatal.9b05221
复制
发表时间：
2020-02-07
期刊：
影响因子：
12.9
通讯作者：
Wu, Ruibo
中科院分区：
文献类型：
--
作者：
Diao, Hongjuan;Chen, Nanhao;Wu, Ruibo
半个多世纪以来，在氧化橙烯环酶(OSC)的催化下，由7个立体中心组成的非环2，3-氧化橙皮烯显著的生化转化为四环羊毛甾醇(胆固醇及其类似物的常见前体)，一直吸引着化学家们的兴趣。尽管已有许多实验和理论报道，但大多数研究都集中在最初的环化反应上，而忽略了随后的级联碳正离子重排和去质子化反应，这些反应决定了最终产物羊毛甾醇的区域和立体化学与胆固醇及其相关结构域的功能相关。在这里，我们继续我们以前关于环化(Angew.Int.Chem.，Int.艾德2015，54,8693-8696)；通过量子力学/分子力学(QM/MM)分子动力学(MD)模拟研究了羊毛甾醇生物合成剩余部分的机理细节，包括三个氢化物转移、两个甲基转移和一个去质子化。我们出手了。
The remarkable biochemical conversion of acyclic 2,3-oxidosqualene to tetracyclic lanosterol (the common precursor to cholesterol and its relatives) with seven stereocenters constructed, catalyzed by oxidosqualene cyclase (OSC), has fascinated chemists for over a half century. Although many experimental and theoretical efforts have been reported, most of the studies focused on the initial cyclization while the subsequent cascade carbocation rearrangement and deprotonation were ignored, which determine the regio- and stereochemistry of the final product lanosterol associated with the function-related structure domains of cholesterol and its relatives. Herein we continue our previous works on the cyclization (Angew. Chem., Int. Ed. 2015, 54, 8693–8696); the mechanistic details of the remaining part of lanosterol biosynthesis, involving three hydride shifts, two methyl shift and one deprotonation, were investigated by quantum mechanical/molecular mechanical (QM/MM) molecular dynamics (MD) simulations. We obt...