Biotechnology Research Center, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo 113-8657 (Japan).
Angew Chem Int Ed Engl. 2015 Mar 27;54(14):4353-6. doi: 10.1002/anie.201411923. Epub 2015 Feb 16.
Terpene cyclization reactions are fascinating owing to the precise control of connectivity and stereochemistry during the catalytic process. Cyclooctat-9-en-7-ol synthase (CotB2) synthesizes an unusual 5-8-5 fused-ring structure with six chiral centers from the universal diterpene precursor, the achiral C20 geranylgeranyl diphosphate substrate. An unusual new mechanism for the exquisite CotB2-catalyzed cyclization that involves a carbon-carbon backbone rearrangement and three long-range hydride shifts is proposed, based on a powerful combination of in vivo studies using uniformly (13)C-labeled glucose and in vitro reactions of regiospecifically deuterium-substituted geranylgeranyl diphosphate substrates. This study shows that CotB2 elegantly demonstrates the synthetic virtuosity and stereochemical control that evolution has conferred on terpene synthases.
萜类化合物的环化反应非常有趣，因为在催化过程中可以精确控制连接和立体化学。环辛-9-烯-7-醇合酶（CotB2）从非手性的 C20 香叶基香叶基二磷酸底物出发，合成了一种不寻常的 5-8-5 稠合环结构，具有六个手性中心。根据使用统一标记的（13）C-葡萄糖的体内研究和对区域特异性氘取代香叶基香叶基二磷酸底物的体外反应的强大结合，提出了 CotB2 催化的环化的一种不寻常的新机制，该机制涉及碳-碳骨架重排和三个远程氢化物转移。这项研究表明，CotB2 巧妙地展示了进化赋予萜烯合酶的合成技巧和立体化学控制。
