Unraveling the serial glycosylation in the biosynthesis of steroidal saponins in the medicinal plant Paris polyphylla and their antifungal action

作     者：Yuegui Chen Qin Yan Yunheng Ji Xue Bai Desen Li Rongfang Mu Kai Guo Minjie Yang Yang Tao Jonathan Gershenzon Yan Liu Shenghong Li Yuegui Chen;Qin Yan;Yunheng Ji;Xue Bai;Desen Li;Rongfang Mu;Kai Guo;Minjie Yang;Yang Tao;Jonathan Gershenzon;Yan Liu;Shenghong Li

作者机构：State Key Laboratory of Phytochemistry and Plant Resources in West ChinaKunming Institute of BotanyChinese Academy of SciencesKunming 650201China State Key Laboratory of Southwestern Chinese Medicine ResourcesInnovative Institute of Chinese Medicine and PharmacyChengdu University of Traditional Chinese MedicineChengdu 611137China Key Laboratory for Plant Diversity and Biogeography of East AsiaKunming Institute of BotanyChinese Academy of SciencesKunming 650201China Max Planck Institute for Chemical EcologyJena D-07745Germany University of Chinese Academy of SciencesBeijing 100049China 

出 版 物：《Acta Pharmaceutica Sinica B》 (药学学报（英文版）)

年 卷 期：2023年第13卷第11期

页      面：4638-4654页

核心收录：

学科分类：1008[医学-中药学(可授医学、理学学位)] 1006[医学-中西医结合] 100602[医学-中西医结合临床] 10[医学] 

基　　金：supported financially by the National Natural Science Foundation of China (Nos.82222072 and U1902214) Yunnan Key Research and Development Program (No.2019ZF011-2,China) the Research Project of Sichuan Province (2022JDJQ0055,China) 

主　　题：Paris polyphylla var.yunnanensis Steroidal saponins Glycosyltransferases Sugar chain elongation Antifungal activity 

摘      要：Sugar-sugar glycosyltransferases play important roles in constructing complex and bioactive ***,we characterized a series of UDP-glycosyltransferases responsible for biosynthesizing the branched sugar chain of bioactive steroidal saponins from a widely known medicinal plant Paris polyphylla *** them,a 2 -O-rhamnosyltransferase and three 6 -O-glucosyltrasferases catalyzed a cascade of glycosylation to produce steroidal diglycosides and triglycosides,*** UDP-glycosyltransferases showed astonishing substrate promiscuity,resulting in the generation of a panel of 24 terpenoid glycosides including 15 previously undescribed compounds.A mutant library containing 44 variants was constructed based on the identification of critical residues by molecular docking simulations and protein model alignments,and a mutant UGT91AH1^(Y187A)with increased catalytic efficiency was *** steroidal saponins exhibited remarkable antifungal activity against four widespread strains of human pathogenic fungi attributed to ergosterol-dependent damage of fungal cell membranes,and 2 -O-rhamnosylation appeared to correlate with strong antifungal *** findings elucidated the biosynthetic machinery for their production of steroidal saponins and revealed their potential as new antifungal agents.