In this opinion, we review some recent work on terpene biosynthesis using multiscale simulation approaches, with special focus on contributions from our group. Terpene synthases generate terpenes employing rich carbocation chemistry, including highly specific ring formations, proton, hydride, methyl, and methylene migrations, followed by reaction quenching. In these enzymes, the main catalytic challenge is not rate enhancement, but rather control of intrinsically reactive carbocations and the resulting product distribution. Herein, we review multiscale simulations of selected mono-, sesqui-, and diterpene synthases. We point to the many tools adopted by terpene synthases to achieve correct substrate fold, carbocation formation, carbocation reaction environment, and reaction quenching. A better understanding of the toolbox employed by terpene synthases is expected to aid in the search for new enzymatic and biomimetic synthetic routes to natural and unnatural terpenes.

中文翻译：

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萜烯合酶产物分布的酶促控制：多尺度模拟的见解。

根据这种观点，我们回顾了使用多尺度模拟方法开展的有关萜烯生物合成的一些最新工作，特别关注了我们小组的贡献。萜烯合酶利用丰富的碳阳离子化学生成萜烯，包括高度特定的环形成，质子，氢化物，甲基和亚甲基迁移，然后反应淬灭。在这些酶中，主要的催化挑战不是提高速率，而是控制内​​在反应性碳正离子和所得产物的分布。在本文中，我们回顾了选定的单萜，倍半萜和二萜合酶的多尺度模拟。我们指出了萜烯合酶采用的许多工具，可实现正确的底物折叠，碳正离子形成，碳正离子反应环境和反应猝灭。