Abstract:
Six oxidosqualene cyclases (NiOSC1-NiOSC6) from Neoalsomitra integrifoliola were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene (1) and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (2). NiOSC1 showed high efficiency in the production of naturally rare (20R)-epimers of oxacyclic triterpenes. Mutagenesis results revealed that the NiOSC1-F731G mutant significantly increased the yields of (20R)-epimers compared to the wild type. Homology modeling and molecular docking elucidated the origin of the (20R)-configuration in the epoxide addition step.
摘要:
来自Neoalsomitraintegrifoliola的六种氧化角鲨烯环化酶(NiOSC1-NiOSC6)被表征为多种三萜支架的生物合成,包括来自2,3-氧化角鲨烯的四环和五环三萜(1)和来自2,3:22,23-二氧化角鲨烯(2)的氧环三萜。NiOSC1在生产天然稀有(20R)的氧杂环三萜差向异构体方面表现出很高的效率。诱变结果显示,与野生型相比,NiOSC1-F731G突变体显著增加了(20R)-差向异构体的产量。同源性建模和分子对接阐明了环氧化物添加步骤中(20R)构型的起源。