Spiroluchuene A Synthase: A Cyclase from Aspergillus luchuensis Forming a Spirotetracyclic Diterpene

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 isotop...

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Published inAngewandte Chemie International Edition Vol. 62; no. 52; pp. e202315659 - n/a
Main Authors Huang, Zheng‐Yu, Taizoumbe, Kizerbo A., Liang, Chengqin, Goldfuss, Bernd, Xu, Jian‐He, Dickschat, Jeroen S.
Format Journal Article
LanguageEnglish
Published Germany Wiley Subscription Services, Inc 21.12.2023
EditionInternational ed. in English
Subjects
Aspergillus - genetics
Aspergillus luchuensis
Biosynthesis
Cyclization
Diterpenes
Enzyme Mechanisms
Hydrocarbons
Isotope labelling
Isotopes
Labeling
Mutagenesis
Radioactive labelling
Spirocycles
Terpenoids
Enzyme Mechanisms
Biosynthesis
Spirocycles
Terpenoids
Isotopes
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Summary: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. A diterpene synthase for spiroluchuene A exhibiting a novel skeleton was discovered from Aspergillus luchuensis. Enzyme engineering through site‐directed mutagenesis allowed for the isolation of spiroluchuene B and the intermediate spiroluchuene. The enzyme mechanism was deeply studied through isotopic labelling experiments, DFT calculations and metadynamic simulations. The thermal reactions of luchudiene were studied.
Bibliography:These authors contributed equally to this work.
ObjectType-Article-1
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content type line 23
ISSN:1433-7851
1521-3773
1521-3773
DOI:10.1002/anie.202315659