Mechanistic analysis for the origin of diverse diterpenes in Tripterygium wilfordii  

作　　者：Lichan Tu Xinbo Cai Yifeng Zhang Yuru Tong Jian Wang Ping Su Yun Lu Tianyuan Hu Yunfeng Luo Xiaoyi Wu Dan Li Luqi Huang Wei Gao 

机构地区：[1]Beijing Shijitan Hospital,Capital Medical University,Beijing 100038,China [2]School of Traditional Chinese Medicine,Capital Medical University,Beijing 100069,China [3]School of Medicine,Zhejiang University City College,Hangzhou 310015,China [4]School of Pharmaceutical Sciences,Capital Medical University,Beijing 100069,China [5]State Key Laboratory Breeding Base of Dao-di Herbs,National Resource Center for Chinese Materia Medica,China Academy of Chinese Medical Sciences,Beijing 100700,China [6]Department of Chemistry,The Scripps Research Institute,Jupiter,FL 33458,USA [7]School of Pharmacy,Hangzhou Normal University,Hangzhou 311121,China

出　　处：《Acta Pharmaceutica Sinica B》2022年第6期2923-2933,共11页药学学报（英文版）

基　　金：supported by the National Key R&D Program of China (No.2020YFA0908000);the Key Project at central government level: The ability establishment of sustainable use for valuable Chinese medicine resources (No.2060302-1806-03);Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D202005)。

摘　　要：Tripterygium wilfordii is a valuable medicinal plant rich in biologically active diterpenoids,but there are few studies on the origins of these diterpenoids in its secondary metabolism.Here,we identified three regions containing tandemly duplicated diterpene synthase genes on chromosomes(Chr) 17 and 21 of T. wilfordii and obtained 11 diterpene synthases with different functions.We farther revealed that these diterpene synthases underwent duplication and rearrangement at approximately 2.3-23.7 million years ago(MYA) by whole-genome triplication(WGT),transposon mediation,and tandem duplication,followed by functional divergence.We first demonstrated that four key amino acids in the sequences of TwCPS3,TwCPS5,and TwCPSS were altered during evolution,leading to their functional divergence and the formation of diterpene secondary metabolites.Then,we demonstrated that the functional divergence of three TwKSLs was driven by mutations in two key amino acids.Finally,we discovered the mechanisms of evolution and pseudogenization of miltiradiene synthases in T.wilfordii and elucidated that the new function in TwMS1/2 from the terpene synthase(TPS)-b subfamily was caused by progressive changes in multiple amino acids after the WGT event.Our results provide key evidence for the formation of diverse diterpenoids during the evolution of secondary metabolites in T.wilfordii.

关 键 词：Tripterygium wilfordii Tandem duplication Diterpene synthases DIVERGENCE Secondary metabolism 

分 类 号：R284[医药卫生—中药学]