Li Heng, Goldfuss Bernd, Dickschat Jeroen S
Kekulé-Institute for Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.
Department for Chemistry, University of Cologne, Greinstraße 4, 50939, Cologne, Germany.
Chemistry. 2025 Apr 22;31(23):e202500712. doi: 10.1002/chem.202500712. Epub 2025 Mar 21.
Four analogs of geranylgeranyl diphosphate (GGPP) with shifted double bonds were synthesised and enzymatically converted with 14 diterpene synthases of previously reported function, including two newly characterised homologs of the benditerpe-2,6,15-triene synthase Bnd4 and the venezuelaene synthase VenA. In successful cases the products were isolated and structurally characterised by NMR spectroscopy, revealing the formation of various diterpenoids with skeletons that have not been reported from natural sources. Isotopic labelling experiments in conjunction with DFT calculations were performed to give insights into hydride migrations in the biosynthesis of the non-natural diterpenes benditerpe-2,7(19),15-triene and venezuelaxenene and their natural counterparts from GGPP.
合成了四种双键位置发生改变的香叶基香叶基二磷酸（GGPP）类似物，并利用14种具有先前报道功能的二萜合酶进行酶促转化，其中包括两种新鉴定的弯二萜-2,6,15-三烯合酶Bnd4和委内瑞拉烯合酶VenA的同源物。在成功的案例中，分离出产物并通过核磁共振光谱对其结构进行表征，揭示了形成了各种具有天然来源未报道骨架的二萜类化合物。结合密度泛函理论计算进行了同位素标记实验，以深入了解非天然二萜弯二萜-2,7(19),15-三烯和委内瑞拉烯以及它们从GGPP衍生的天然对应物生物合成过程中的氢化物迁移情况。
