武汉大学Tiangang LiuLiu、德国弗里德里希威伦大学Jeroen S. Dickschat和日本东京大学Ikuro Abe共同合作取得重要工作进展，他们研究发现了非角鲨烯三萜类化合物。相关论文2022年6月1日在线发表于《自然》杂志。
所有已知的三萜都是由角鲨烯或氧化角鲨烯的三萜合酶 (TrTS) 产生的。这种方法与由聚异戊二烯二磷酸形成的短链 (C10–C25) 萜烯的生物合成根本不同。在这项研究中，研究人员对两种真菌来源的I型嵌合萜类合酶TvTS和MpMS进行了表征。这两种酶都使用二甲基烯丙基二磷酸和异戊烯二磷酸或六戊二烯二磷酸作为底物，代表了非角鲨烯依赖性三萜生物合成的第一个例子。
在同位素标记实验中研究了TvTS和MpMS的环化机制及其产物的绝对构型。通过TvTS和全MpMS的萜烯环化酶结构域的结构分析，可以进一步了解它们的催化机制。研究人员开发了一个基于AlphaFold2 的筛选平台来挖掘第三种TrTS，即炭疽菌胶萜醇合酶 (CgCS)。他们的研究结果确定了三萜生物合成的新酶促机制，并增强了对自然界中萜生物合成的理解。
附：英文原文
Title: Discovery of non-squalene triterpenes
Author: Tao, Hui, Lauterbach, Lukas, Bian, Guangkai, Chen, Rong, Hou, Anwei, Mori, Takahiro, Cheng, Shu, Hu, Ben, Lu, Li, Mu, Xin, Li, Min, Adachi, Naruhiko, Kawasaki, Masato, Moriya, Toshio, Senda, Toshiya, Wang, Xinghuan, Deng, Zixin, Abe, Ikuro, Dickschat, Jeroen S., Liu, Tiangang
Issue&Volume: 2022-06-01
Abstract: All known triterpenes are generated by triterpene synthases (TrTSs) from squalene or oxidosqualene1. This approach is fundamentally different from the biosynthesis of short-chain (C10–C25) terpenes that are formed from polyisoprenyl diphosphates2,3,4. In this study, two fungal chimeric class I TrTSs, Talaromyces verruculosus talaropentaene synthase (TvTS) and Macrophomina phaseolina macrophomene synthase (MpMS), were characterized. Both enzymes use dimethylallyl diphosphate and isopentenyl diphosphate or hexaprenyl diphosphate as substrates, representing the first examples, to our knowledge, of non-squalene-dependent triterpene biosynthesis. The cyclization mechanisms of TvTS and MpMS and the absolute configurations of their products were investigated in isotopic labelling experiments. Structural analyses of the terpene cyclase domain of TvTS and full-length MpMS provide detailed insights into their catalytic mechanisms. An AlphaFold2-based screening platform was developed to mine a third TrTS, Colletotrichum gloeosporioides colleterpenol synthase (CgCS). Our findings identify a new enzymatic mechanism for the biosynthesis of triterpenes and enhance understanding of terpene biosynthesis in nature.
DOI: 10.1038/s41586-022-04773-3
Source: https://www.nature.com/articles/s41586-022-04773-3
Nature：《自然》，创刊于1869年。隶属于施普林格·自然出版集团，最新IF：69.504
官方网址：http://www.nature.com/
投稿链接：http://www.nature.com/authors/submit_manuscript.html
本期文章：《自然》：Online/在线发表
