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Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene |
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| Authors: | Zheng-Yu Huang Kizerbo A. Taizoumbe Prof. Dr. Chengqin Liang Prof. Dr. Bernd Goldfuss Prof. Dr. Jian-He Xu Prof. Dr. Jeroen S. Dickschat |
| Affiliation: | 1. State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, East China University of Science and Technology, Shanghai, 200237 China These authors contributed equally to this work.;2. Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany These authors contributed equally to this work.;3. College of Pharmacy, Guilin Medical University, Guilin, 541004 China;4. Department of Chemistry, University of Cologne, Greinstraße 4, 50939 Cologne, Germany;5. State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, East China University of Science and Technology, Shanghai, 200237 China;6. Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany |
| Abstract: | The diterpene synthase AlTS was identified from Aspergillus luchuensis. AlTS catalyses the formation of the diterpene hydrocarbon spiroluchuene A, which exhibits a novel skeleton characterised by a spirocyclic ring system. The cyclisation mechanism towards this compound was elucidated through isotopic labelling experiments in conjunction with DFT calculations and metadynamic simulations. The biosynthetic intermediate luchudiene, besides the derivative spiroluchuene B, was captured from an enzyme variant obtained through site-directed mutagenesis. With its 10-membered ring luchudiene is structurally related to germacrenes and can undergo a Cope rearrangement to luchuelemene. |
| Keywords: | Biosynthesis Enzyme Mechanisms Isotopes Spirocycles Terpenoids |