德国波恩大学Jeroen S.研究团队报道了钠多芬生物合成中的片段化和[4+3]环加成。相关研究成果发表在2023年5月29日出版的国际学术期刊《自然—化学》。

萜烯是最大的一类天然产物。它们的骨架是由萜烯环化酶（TC）通过复杂的酶促转化从无环低聚丙烯基二磷酸盐中形成的。这些酶反应从通过二磷酸提取的底物电离开始，然后通过阳离子中间体进行级联反应。基于同位素标记实验和计算研究，研究人员提出了土壤细菌沙雷氏菌的高甲基化倍半萜钠多芬的环化机制。其生物合成中的一个特殊问题在于由链亚甲基碳形成几个甲基。

潜在的机制涉及甲基转移酶介导的环化和前所未有的环收缩，碳从链中挤出形成甲基。萜烯环化酶随后催化裂解成两个反应性中间体，然后在它们之间进行氢转移，并通过[4+3]环加成使片段重组。

该研究解决了钠多芬生物合成中额外甲基形成的复杂机制问题。

附：英文原文

Title: Fragmentation and [4+3] cycloaddition in sodorifen biosynthesis

Author: Xu, Houchao, Lauterbach, Lukas, Goldfuss, Bernd, Schnakenburg, Gregor, Dickschat, Jeroen S.

Issue&Volume: 2023-05-29

Abstract: Terpenes constitute the largest class of natural products. Their skeletons are formed by terpene cyclases (TCs) from acyclic oligoprenyl diphosphates through sophisticated enzymatic conversions. These enzyme reactions start with substrate ionization through diphosphate abstraction, followed by a cascade reaction via cationic intermediates. Based on isotopic-labelling experiments in combination with a computational study, the cyclization mechanism for sodorifen, a highly methylated sesquiterpene from the soil bacterium Serratia plymuthica, was resolved. A peculiar problem in its biosynthesis lies in the formation of several methyl groups from chain methylene carbons. The underlying mechanism involves a methyltransferase-mediated cyclization and unprecedented ring contraction with carbon extrusion from the chain to form a methyl group. A terpene cyclase subsequently catalyses a fragmentation into two reactive intermediates, followed by hydrogen transfers between them and recombination of the fragments by [4+3] cycloaddition. This study solves the intricate mechanistic problem of extra methyl group formation in sodorifen biosynthesis.

DOI: 10.1038/s41557-023-01223-z

Source: https://www.nature.com/articles/s41557-023-01223-z