Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts

doi:10.1016/j.ymben.2015.03.003

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	Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts
	Wang, Pingping 2; Wei, Yongjun 2; Fan, Yun 1,2,4; Liu, Qunfang3 ; Wei, Wei 2; Yang, Chengshuai 2; Zhang, Lei 2; Zhao, Guoping 1,2,4; Yue, Jianmin3 ; Yan, Xing 2
刊名	METABOLIC ENGINEERING
	2015-05
卷号	29 页码:97-105
关键词	Ginsenoside Rh2 Ginsenoside Rg3 UDP-glycosyltransferase Protopanaxadiol producing chassis Panax plants
ISSN号	1096-7176
DOI	10.1016/j.ymben.2015.03.003
文献子类	Article
英文摘要	Ginsenosides Rh2 and Rg3 represent promising candidates for cancer prevention and therapy and have low toxicity. However, the concentrations of Rh2 and Rg3 are extremely low in the bioactive constituents (triterpene saponins) of ginseng. Despite the available heterologous biosynthesis of their aglycone (protopanaxadiol, PPD) in yeast, production of Rh2 and Rg3 by a synthetic biology approach was hindered by the absence of bioparts to glucosylate the C3 hydroxyl of PPD. In this study, two UDP-glycosyltransferases (UGTs) were cloned and identified from Panax ginseng. UGTPg45 selectively transfers a glucose moiety to the C3 hydroxyl of PPD and its ginsenosides. UGTPg29 selectively transfers a glucose moiety to the C3 glucose of Rh2 to form a 1-2-glycosidic bond. Based on the two UGTs and a yeast chassis to produce PPD, yeast cell factories were built to produce Rh2 and/or Rg3 from glucose. The turnover number (k(cat)) of UGTPg29 was more than 2500-fold that of UGTPg45, which might explain the higher Rg3 yield than that of Rh2 in the yeast cell factories. Building yeast cell factories to produce Rh2 or Rg3 from simple sugars by microbial fermentation provides an alternative approach to replace the traditional method of extracting ginsenosides from Panax plants. (C) 2015 International Metabolic Engineering Society. Published by Elsevier Inc. All rights reserved.
资助项目	National Basic Research Program of China[2012CB721103] ; National Basic Research Program of China[2012CB721105] ; Knowledge Innovation Program from the Chinese Academy of Sciences[KSCX2-EW-G-13-1] ; Knowledge Innovation Program from the Chinese Academy of Sciences[KSCX2-EW-J-12]
WOS关键词	SACCHAROMYCES-CEREVISIAE ; 20(S)-GINSENOSIDE RG3 ; PANAX-GINSENG ; DAMMARENEDIOL-II ; CANCER CELLS ; RH-2 ; EXPRESSION ; SAPONINS ; PATHWAY ; RG(3)
WOS研究方向	Biotechnology & Applied Microbiology
语种	英语
出版者	ACADEMIC PRESS INC ELSEVIER SCIENCE
WOS记录号	WOS:000354123900010
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/276551]
专题	天然药物化学研究室中科院受体结构与功能重点实验室新药研究国家重点实验室
通讯作者	Yue, Jianmin
作者单位	1.Fudan Univ, Sch Life Sci, Dept Microbiol, State Key Lab Genet Engn, Shanghai 200433, Peoples R China; 2.Chinese Acad Sci, CAS Key Lab Synthet Biol, Inst Plant Physiol & Ecol, Shanghai Inst Biol Sci, Shanghai 200032, Peoples R China; 3.Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; 4.Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China
推荐引用方式 GB/T 7714	Wang, Pingping,Wei, Yongjun,Fan, Yun,et al. Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts[J]. METABOLIC ENGINEERING,2015,29:97-105.
APA	Wang, Pingping.,Wei, Yongjun.,Fan, Yun.,Liu, Qunfang.,Wei, Wei.,...&Zhou, Zhihua.(2015).Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts.METABOLIC ENGINEERING,29,97-105.
MLA	Wang, Pingping,et al."Production of bioactive ginsenosides Rh2 and Rg3 by metabolically engineered yeasts".METABOLIC ENGINEERING 29(2015):97-105.