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Crystal Structure Based Mutagenesis of Cattleyene Synthase Leads to the Generation of Rearranged Polycyclic Diterpenes

Baiying Xing, Houchao Xu, Annan Li, Tingting Lou, Meng Xu, Kaibiao Wang, Zhengren Xu, Jeroen S. Dickschat, Donghui Yang, Ming Ma

2022Angewandte Chemie International Edition30 citationsDOIOpen Access PDF

Abstract

Abstract The crystal structures of cattleyene synthase (apo‐CyS), and CyS complexed with geranylgeranyl pyrophosphate (GGPP) were solved. The CyS C59A variant exhibited an increased production of cattleyene and other diterpenes with diverse skeletons. Its structure showed a widened active site cavity explaining the relaxed selectivity. Isotopic labeling experiments revealed a remarkable cyclization mechanism involving several skeletal rearrangements for one of the novel diterpenes.

Topics & Concepts

ChemistryMutagenesisStereochemistryATP synthaseDiterpenePyrophosphateCrystal structureBiosynthesisBiochemistryEnzymeCrystallographyGeneMutationPlant biochemistry and biosynthesisMicrobial Natural Products and BiosynthesisNatural product bioactivities and synthesis