Biochemical and Metabolic Insights into Hyoscyamine Dehydrogenase

doi:10.1021/acscatal.0c04667

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	Biochemical and Metabolic Insights into Hyoscyamine Dehydrogenase
	Qiu,Fei ; Yan,Yijun ; Zeng,Junlan ; Huang,Jian-Ping ; Zeng,Lingjiang ; Zhong,Wei ; Lan,Xiaozhong ; Chen,Min ; Huang,Sheng-Xiong ; Liao,Zhihua
	2021
发表期刊	ACS CATALYSIS
ISSN	2155-5435
卷号	11 期号:5 页码:2912-2924
摘要	Hyoscyamine, a member of the class of compounds known as tropane alkaloids (TAs), is clinically used as an anticholinergic drug. Previous research has predicted that hyoscyamine is produced via the reduction of hyoscyamine aldehyde. In this study, we identified a root-expressed gene from Atropa belladonna, named AbHDH, which encodes a hyoscyamine dehydrogenase involved in the formation of hyoscyamine. Enzymatic assays indicated that AbHDH was able to not only reduce hyoscyamine aldehyde to produce hyoscyamine but also oxidize hyoscyamine to form hyoscyamine aldehyde under different conditions. To elucidate its catalytic mechanism, the crystal structure of AbHDH at a 2.4-A resolution was also determined. Overexpression of AbHDH significantly enhanced the biosynthesis of hyoscyamine and the production of anisodamine and scopolamine in root cultures of A. belladonna. However, suppression of AbHDH using RNAi technology did not reduce the production of hyoscyamine, anisodamine, or scopolamine, though it did increase the accumulation of hyoscyamine aldehyde. In summary, this study provided timely biochemical and metabolic insights into hyoscyamine dehydrogenase, pointing to an alternative, promising way to produce pharmaceutical TAs via metabolic engineering in planta.
关键词	biosynthesis crystal structure hyoscyamine hyoscyamine dehydrogenase metabolic engineering TROPANE ALKALOID BIOSYNTHESIS TRANSGENIC ATROPA-BELLADONNA POLYKETIDE SYNTHASE ROOT CULTURES SCOPOLAMINE PUTRESCINE PLANTS 6-BETA-HYDROXYLASE CYTOCHROME-P450 PATHWAY
DOI	10.1021/acscatal.0c04667
WOS记录号	WOS:000626844200041
引用统计	被引频次：19[WOS] [WOS记录] [WOS相关记录]
文献类型	期刊论文
条目标识符	http://ir.kib.ac.cn/handle/151853/73483
专题	中国科学院昆明植物研究所
作者单位	1.Southwest Univ, SWU TAAHC Med Plant Joint R&D Ctr, Chongqing Key Lab Plant Resource Conservat & Germ, Sch Life Sci,Minist Educ,Key Lab Ecoenvironm Thre, Chongqing 400715, Peoples R China 2.Chinese Acad Sci, State Key Lab Phytochem & Plant Resources West Ch, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China 3.Chinese Acad Sci, CAS Ctr Excellence Mol Plant Sci, Kunming Inst Bot, Kunming 650201, Yunnan, Peoples R China 4.Xizang Agr & Anim Husb Coll, TAAHC SWU Med Plant Joint R&D Ctr, Tibetan Collaborat Innovat Ctr Agr & Anim Husb Re, Nyingchi Of Tibet 860000, Peoples R China 5.Southwest Univ, Minist Educ, Key Lab Luminescent & Real Time Analyt Chem, Coll Pharmaceut Sci, Chongqing 400715, Peoples R China
推荐引用方式 GB/T 7714	Qiu,Fei,Yan,Yijun,Zeng,Junlan,et al. Biochemical and Metabolic Insights into Hyoscyamine Dehydrogenase[J]. ACS CATALYSIS,2021,11(5):2912-2924.
APA	Qiu,Fei.,Yan,Yijun.,Zeng,Junlan.,Huang,Jian-Ping.,Zeng,Lingjiang.,...&Liao,Zhihua.(2021).Biochemical and Metabolic Insights into Hyoscyamine Dehydrogenase.ACS CATALYSIS,11(5),2912-2924.
MLA	Qiu,Fei,et al."Biochemical and Metabolic Insights into Hyoscyamine Dehydrogenase".ACS CATALYSIS 11.5(2021):2912-2924.

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