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Discovery of non-squalene triterpenes.
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.
Affiliation
  • Tao H; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Lauterbach L; Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Bian G; Department of Urology, Zhongnan Hospital of Wuhan University, School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Chen R; Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Hou A; Kekulé-Institut für Organische Chemie und Biochemie, Rheinische Friedrich-Wilhelms-Universität Bonn, Bonn, Germany.
  • Mori T; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan.
  • Cheng S; Collaborative Research Institute for Innovative Microbiology, The University of Tokyo, Tokyo, Japan.
  • Hu B; PRESTO, Japan Science and Technology Agency, Saitama, Japan.
  • Lu L; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Mu X; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Li M; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Adachi N; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Kawasaki M; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Moriya T; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
  • Senda T; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
  • Wang X; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
  • Deng Z; Structural Biology Research Center, Institute of Materials Structure Science, High Energy Accelerator Research Organization (KEK), Tsukuba, Japan.
  • Abe I; Department of Urology, Zhongnan Hospital of Wuhan University, Wuhan, China.
  • Dickschat JS; Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education and School of Pharmaceutical Sciences, Wuhan University, Wuhan, China.
  • Liu T; Graduate School of Pharmaceutical Sciences, The University of Tokyo, Tokyo, Japan. abei@mol.f.u-tokyo.ac.jp.
Nature ; 606(7913): 414-419, 2022 06.
Article in En | MEDLINE | ID: mdl-35650436
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 diphosphates2-4. 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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ascomycota / Triterpenes / Talaromyces Type of study: Prognostic_studies Language: En Journal: Nature Year: 2022 Type: Article Affiliation country: Japan
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Ascomycota / Triterpenes / Talaromyces Type of study: Prognostic_studies Language: En Journal: Nature Year: 2022 Type: Article Affiliation country: Japan