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Published on: October 3, 2018
Characterization and mechanistic insights of a novel (1(10)E,4E,6R,7S)-germacradien-6-ol synthase from Senecio
Yang Zou1, Jun Xie1, Jingyi Li1
1State Key Laboratory of Bioactive Substance and Function of Natural Medicines, NHC Key Laboratory of Biosynthesis of Natural Products, CAMS Key Laboratory of Enzyme and Biocatalysis of Natural Drugs, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, 100050, China.
Abstract:
A sesquiterpene synthase from Senecio scandens (SsTPS2) specifically catalyzes the formation of (1(10)E,4E,6R,7S)-germacradien-6-ol, an enantiomer of the known bacterial product. This is the first confirmed synthase affording such a 7S germacrane-type skeleton. A single point mutation (Y404S) switches enzymatic product to (4S,7S)-germacrene D-4-ol. Isotope studies indicate a 1,3-hydride shift before water quenching and docking studies explain residue control over product outcomes. (1(10)E,4E,6R,7S)-germacradien-6-ol and its enantiomer significantly inhibit NO production in LPS-induced RAW264.7 macrophages, displaying potent anti-inflammatory activity.
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Reaction Mechanisms
For instance, the decomposition of ozone appears to follow a mechanism with two steps:
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