Zev Shani, Ringel Marion, Driller Ronja, Loll Bernhard, Brück Thomas, Major Dan T
Department of Chemistry and Institute for Nanotechnology & Advanced Materials, Bar-Ilan University, Ramat-Gan 52900, Israel.
Werner Siemens Chair of Synthetic Biotechnology, Department of Chemistry, Technical University of Munich, Lichtenbergstraße 4, 85748 Garching, Germany.
Beilstein J Org Chem. 2022 Aug 4;18:972-978. doi: 10.3762/bjoc.18.97. eCollection 2022.
Terpene synthases are responsible for the biosynthesis of terpenes, the largest family of natural products. Hydropyrene synthase generates hydropyrene and hydropyrenol as its main products along with two byproducts, isoelisabethatrienes A and B. Fascinatingly, a single active site mutation (M75L) diverts the product distribution towards isoelisabethatrienes A and B. In the current work, we study the competing pathways leading to these products using quantum chemical calculations in the gas phase. We show that there is a great thermodynamic preference for hydropyrene and hydropyrenol formation, and hence most likely in the synthesis of the isoelisabethatriene products kinetic control is at play.
萜烯合酶负责萜类化合物的生物合成，萜类是最大的天然产物家族。氢化芘合酶以氢化芘和氢化芘醇作为主要产物，同时还有两种副产物，异伊丽沙白三烯A和B。有趣的是，单个活性位点突变（M75L）会使产物分布转向异伊丽沙白三烯A和B。在当前的工作中，我们在气相中使用量子化学计算研究了导致这些产物的竞争途径。我们表明，形成氢化芘和氢化芘醇在热力学上具有很大的优势，因此在异伊丽沙白三烯产物的合成中，很可能起作用的是动力学控制。
