Department of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan 52900, Israel.
Department of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan 52900, Israel.
Curr Opin Biotechnol. 2020 Oct;65:248-258. doi: 10.1016/j.copbio.2020.06.002. Epub 2020 Jul 14.
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.
在这篇观点文章中，我们回顾了一些最近使用多尺度模拟方法研究萜类生物合成的工作，特别关注了我们小组的贡献。萜烯合酶利用丰富的碳正离子化学生成萜类化合物，包括高度特异性的环形成、质子、氢化物、甲基和亚甲基迁移，然后进行反应猝灭。在这些酶中，主要的催化挑战不是提高反应速率，而是控制内在反应性的碳正离子和由此产生的产物分布。在此，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，以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。更好地理解萜烯合酶所采用的工具包有望有助于寻找新的酶促和仿生合成途径，以获得天然和非天然萜类化合物。
