Deracemization of 2-Methyl-1,2,3,4-Tetrahydroquinoline Using Mutant Cyclohexylamine Oxidase Obtained by Iterative Saturation Mutagenesis

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	Deracemization of 2-Methyl-1,2,3,4-Tetrahydroquinoline Using Mutant Cyclohexylamine Oxidase Obtained by Iterative Saturation Mutagenesis
	Li, Guangyue 1,2; Ren, Jie 1,2; Yao, Peiyuan 1,2; Duan, Yitao 1,2; Zhang, Hailing 1,2; Wu, Qiaqing 1,2; Feng, Jinhui 1,2; Lau, Peter C. K.3,4,5,6; Zhu, Dunming 1,2
刊名	ACS CATALYSIS
	2014-03-01
卷号	4 期号:3 页码:903-908
关键词	biocatalysis amine oxidase iterative saturation mutagenesis chiral amines deracemization
英文摘要	The current toolkit of biocatalysts for the production of enantiomerically pure chiral amines is largely restricted to amine transaminases, ammonia lyases, or the genetic variants of monoamine oxidase N(MAO-N) from Aspergillus niger. Flavin-dependent amine oxidases have the apparent advantage of using molecular oxygen as a stoichiometric oxidant and their reactions are irreversible. To expand the toolkit and increase the substrate spectrum of a bacterial and flavin-dependent cyclohexylamine oxidase (CHAO) to enable deracemization of secondary amines, saturation mutagenesis of 11 amino acid residues located around the cyclohexanone substrate within a distance of 5 angstrom, followed by iterative saturation mutagenesis of four beneficial mutants, were performed. Screening with 2-methyl-1,2,3,4-tetrahydroquinoline as the substrate generated two improved CHAO variants, T198FL199S and T198FL199SM226F, that exhibited up to 406 times higher catalytic efficiency than the wild-type CHAO. Besides, high stereoselectivity for 2-methyl-1,2,3,4-tetrahydroquinoline and other 2-substituted-1,2,3,4-tetrahydroquinolines was demonstrated. In particular, deracemization of 2-methyl-1,2,3,4-tetrahydroquinoline by Escherichia coli whole cells expressing CHAO mutant T198FL199SM226F led to the production of (R)-2-methyl-1,2,3,4-tetrahydroquinoline with high yield (76%) and enantiomeric excess (ee, 9896). Tetrahydroquinolines are important building blocks of natural and synthetic products useful in the pharmaceutical and agrochemical industries.
WOS标题词	Science & Technology ; Physical Sciences
类目[WOS]	Chemistry, Physical
研究领域[WOS]	Chemistry
关键词[WOS]	HIGHLY ENANTIOSELECTIVE HYDROGENATION ; BREVIBACTERIUM-OXYDANS IH-35A ; PROTEIN FARNESYLTRANSFERASE ; ASYMMETRIC HYDROGENATION ; QUINOLINE ; BIOCATALYSIS ; DERIVATIVES ; PURIFICATION ; MODULATORS ; INHIBITORS
收录类别	SCI
语种	英语
WOS记录号	WOS:000332756700021
内容类型	期刊论文
源URL	[http://124.16.173.210/handle/834782/1411]
专题	天津工业生物技术研究所_生物催化与绿色化工朱敦明_期刊论文
作者单位	1.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Natl Engn Lab Ind Enzymes, Tianjin Airport Econ Area, Tianjin 300308, Peoples R China 2.Chinese Acad Sci, Tianjin Inst Ind Biotechnol, Tianjin Engn Ctr Biocatalyt Technol, Tianjin Airport Econ Area, Tianjin 300308, Peoples R China 3.Natl Res Council Canada, Montreal, PQ H4P 2R2, Canada 4.McGill Univ, Dept Chem, Montreal, PQ H3A 2B4, Canada 5.McGill Univ, Dept Microbiol & Immunol, Montreal, PQ H3A 2B4, Canada 6.FQRNT Ctr Green Chem & Catalysis, Montreal, PQ, Canada
推荐引用方式 GB/T 7714	Li, Guangyue,Ren, Jie,Yao, Peiyuan,et al. Deracemization of 2-Methyl-1,2,3,4-Tetrahydroquinoline Using Mutant Cyclohexylamine Oxidase Obtained by Iterative Saturation Mutagenesis[J]. ACS CATALYSIS,2014,4(3):903-908.
APA	Li, Guangyue.,Ren, Jie.,Yao, Peiyuan.,Duan, Yitao.,Zhang, Hailing.,...&Zhu, Dunming.(2014).Deracemization of 2-Methyl-1,2,3,4-Tetrahydroquinoline Using Mutant Cyclohexylamine Oxidase Obtained by Iterative Saturation Mutagenesis.ACS CATALYSIS,4(3),903-908.
MLA	Li, Guangyue,et al."Deracemization of 2-Methyl-1,2,3,4-Tetrahydroquinoline Using Mutant Cyclohexylamine Oxidase Obtained by Iterative Saturation Mutagenesis".ACS CATALYSIS 4.3(2014):903-908.