Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant

doi:10.1016/j.ijbiomac.2018.06.046

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	Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant
	Li, Wei 1,3; Yang, Yun 1,3; Qiao, Chong 1,3; Zhang, Guolin 3; Luo, Yinggang 2,3
刊名	INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES
	2019-10-01
卷号	117 期号:2018 页码:1264-1279
关键词	Lycoris radiata Galanthamine Phenylalanine ammonia-lyase Cinnamate 4-hydroxylase Biosynthesis
ISSN号	0141-8130
DOI	10.1016/j.ijbiomac.2018.06.046
产权排序	1
文献子类	Article
英文摘要	Galanthamine (GAL), the well-known Amaryllidaceae alkaloid, is a clinically used drug for the treatment of Alzheimer's disease. L-Phenylalanine (Phe) and trans-cinnamic acid (CA) were enzymatically transformed into the catechol portion of GAL Herein, a Phe ammonia-lyase-encoding gene LrPAL3 and a cinnamate 4hydroxylase-encoding gene LrC4H were cloned from Lycoris radiata, a GAL-producing plant. LrPAL3 was overexpressed in Escherichia coli and purified to homogeneity. LrPAL3 catalyzes the forward deamination conversion of L-Phe into trans-CA. The 3-chloro- and 4-fluoro-L-Phe were deaminated to generate the corresponding 3-chloro- and 4-fluoro-trans-CA by LrPAL3. LrPAL3-catalyzed reverse hydroamination was confirmed by the conversion of trans-CA into L-Phe with exceptional regio- and stereo-selectivity. LrC4H was overexpressed in E. coli with tCamCPR, a cytochrome P450 reductase-encoding gene. LrC4H catalyzes the regioselective parahydroxylation on trans-CA to form p-coumaric acid. The transcriptional levels of both LrPAL3 and LrC4H were positively associated with the GAL contents within the leaves and flowers of L radiata, which suggested that their expression and function are co-regulated and involved in the biosynthesis of GAL The present investigations on the biosynthetic genes of GAL will promote the development of synthetic biology platforms for this kind of important drug via metabolic engineering. (C) 2018 Elsevier B.V. All rights reserved.
学科主题	Biochemistry ; Biophysics
URL标识	查看原文
WOS关键词	AMARYLLIDACEAE ALKALOIDS ; AMINO-ACIDS ; BIOSYNTHESIS ; MECHANISM ; ENZYME ; BINDING ; CYTOCHROME-P450 ; NORBELLADINE ; BIOCATALYSIS ; AMINOMUTASE
WOS研究方向	Biochemistry & Molecular Biology ; Chemistry ; Polymer Science
语种	英语
出版者	ELSEVIER SCIENCE BV
WOS记录号	WOS:000442057700144
内容类型	期刊论文
源URL	[http://210.75.237.14/handle/351003/30148]
专题	国家天然药物工程技术研究中心_天然产物研究
作者单位	1.Univ Chinese Acad Sci, 19A Yuquan Rd, Beijing 100049, Peoples R China 2.Chinese Acad Sci, Shanghai Inst Organ Chem, State Key Lab Bioorgan & Nat Prod Chem, Shanghai 200032, Peoples R China; 3.Chinese Acad Sci, Chengdu Inst Biol, Ctr Nat Prod Res, 9 Sect 4,Renmin Rd South, Chengdu 610041, Sichuan, Peoples R China;
推荐引用方式 GB/T 7714	Li, Wei,Yang, Yun,Qiao, Chong,et al. Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant[J]. INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,2019,117(2018):1264-1279.
APA	Li, Wei,Yang, Yun,Qiao, Chong,Zhang, Guolin,&Luo, Yinggang.(2019).Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant.INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES,117(2018),1264-1279.
MLA	Li, Wei,et al."Functional characterization of phenylalanine ammonia-lyase- and cinnamate 4-hydroxylase-encoding genes from Lycoris radiata, a galanthamine-producing plant".INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES 117.2018(2019):1264-1279.