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螺旋鲁库烯 A 合酶:来自土曲霉的环化酶,形成螺四环二萜。

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

机构信息

State Key Laboratory of Bioreactor Engineering, Shanghai Collaborative Innovation Centre for Biomanufacturing, East China University of Science and Technology, Shanghai, 200237, China.

Kekulé-Institute of Organic Chemistry and Biochemistry, University of Bonn, Gerhard-Domagk-Straße 1, 53121, Bonn, Germany.

出版信息

Angew Chem Int Ed Engl. 2023 Dec 21;62(52):e202315659. doi: 10.1002/anie.202315659. Epub 2023 Nov 27.

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.

摘要

从点青霉属(Aspergillus luchuensis)中鉴定出二萜合酶 AlTS。AlTS 催化二萜烃螺六氢南美烯 A 的形成,其具有新颖的骨架,其特征在于螺环系统。通过与 DFT 计算和元动力学模拟相结合的同位素标记实验,阐明了该化合物的环化机制。通过定点突变获得的酶变体,捕获了生物合成中间体六氢南美烯,以及衍生物螺六氢南美烯 B。十元环六氢南美烯与金合欢烯结构相关,可发生 Cope 重排形成六氢南美衣烯。

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