人参皂苷生物合成和次生代谢工程

中国生物工程杂志

2009, Vol. 29

Issue (10): 102-108

综述

人参皂苷生物合成和次生代谢工程

吴琼,周应群,孙超,陈士林^**

中国医学科学院/北京协和医学院药用植物研究所北京 1000193

Progress in Ginsenosides Biosynthesis and Prospect of the Secondary Metabolic Engineering for the Production of Ginsenosides

WU Qiong ,ZHOU Ying-qun,SUN Chao,CHEN Shi-lin

Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Beijing 100193,China

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摘要：

人参皂苷属于植物三萜皂苷类化合物，是传统名贵药材人参和西洋参的主要活性成分，具有抗炎、抗氧化作用，还有广泛的抗肿瘤作用。人参皂苷与植物甾醇共享前期代谢途径，通过2, 3-氧化鲨烯环化步骤进入三萜代谢分支途径，在三萜碳环骨架复杂修饰的基础上形成人参皂苷。综述了近年人参皂苷生物合成途径及关键酶基因研究的最新进展，揭示了人参皂苷生物合成的基本途径，对途径中关键酶的基因进行了综述，并结合次生代谢工程技术, 探讨了该技术在人参皂苷生物合成中的应用前景。

关键词： 人参皂苷; 生物合成; 关键酶; 代谢工程

Abstract:

Ginsenosides, which belongs to triterpenoid saponins of plant terpenoids, are the main active components of the valuable medicinal herbs ginseng and American ginseng. Recent studies show that ginsenosides have a variety of beneficial effects, including anti-inflamatory, antioxidant, and anticancer effects. Ginsenosides are synthesized by complicated modification of triterpenoid skeleton after cyclization of 2,3-oxidosqualene through triterpene saponin synthesis pathway in which they share common early steps with phytosterols synthesis.It outlines recent advances for the biosynthesis of ginsenosides, the cloning and characterization of genes encoding key enzymes in the pathway and the basal framework of ginsenosides biosynthesis pathway. The prospects of secondary metabolism engineering in the biosynthesis of plant natural products and its application in ginsenosides biosynthesis are also discussed.

Key words: Ginsenosides Biosynthesis Key enzymes Metabolism engineering

收稿日期: 2009-06-08 出版日期: 2009-10-29

ZTFLH:

Q819

基金资助:

国家自然科学基金(30873459)资助项

通讯作者: 陈士林 E-mail: slchen@implad.ac.cn

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引用本文:

吴琼周应群孙超陈士林. 人参皂苷生物合成和次生代谢工程[J]. 中国生物工程杂志, 2009, 29(10): 102-108.

TUN Qiong, ZHOU Ying-Qun, SUN Chao, CHEN Shi-Lin. Progress in Ginsenosides Biosynthesis and Prospect of the Secondary Metabolic Engineering for the Production of Ginsenosides. China Biotechnology, 2009, 29(10): 102-108.

链接本文:

https://manu60.magtech.com.cn/biotech/CN/ 或 https://manu60.magtech.com.cn/biotech/CN/Y2009/V29/I10/102

［1］	李方元. 中国人参和西洋参中国农业科学技术出版社, 2002 Li F Y. Chinese Ginseng and American Ginseng. Beijing: China Agricultural Science and Technology Press, 2002
［2］	Shibata S. Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Korean Med Sci, 2001, 16(Suppl): S28~37
［3］	Bach T J, Boronat A, Caelles C, et al. Aspects related to mevalonate biosynthesis in plants. Lipids, 1991, 26(8): 637~648
［4］	RamosValdivia A C, Heijden R V D, Verpoorte R. Isopentenyl diphosphate isomerase: a core enzyme in isoprenoid biosynthesis. A review of its biochemistry and function. Nat Prod Rep, 1997,14(6):591~603
［5］	Suzuki H, Achnine L, Xu R, et al. A genomics approach to the early stages of triterpene saponin biosynthesis in Medicago truncatula. Plant J, 2002, 32: 1033~1048
［6］	Lee M H, Jeong J H, Seo J W, et al. Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol, 2004, 45(8): 976~984
［7］	Choi D W, Jung J, Ha Y I, et al. Analysis of transcripts in methyl jasmanatetreated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenoides and other secondary metabolites. Plant Cell Rep, 2005, 23: 557~566
［8］	Haralampidis K, Trojanowska M, Osbourn A E. Biosynthesis of triterpenoid saponins in plants. Adv Biochem Eng Biotechnol, 2002, 75: 31~49
［9］	Pimpimon Tansakul M S, Tetsuo Kushiro, Yutaka Ebizuka. DammarenediolII synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Letters, 2006, 580: 5143~5149
［10］	Mohammad Basyuni H O, Etsuko Tsujimoto. Triterpene synthases from the Okinawan mangrove tribe, Rhizophoraceae. FEBS Journal, 2007, 274: 5028~5042
［11］	Kushiro T, Shibuya M, Ebizuka Y. Beta-Amyrin synthase: Cloning of oxidosqualene cyclase that catalyzes the formation of the most popular triterpene among higher plants. Eur J Biochem, 1998, 256: 238~244
［12］	Kushiro T S M, Ebizuka Y. Molecular cloning of oxidosqualene cyclase cDNA from Panax ginseng: the isogene that encodes betaamyrin synthase. Towards natural medicine research in the 21st century, Excerpta Medica International Congress Series, 1998, 1157: 421~428
［13］	Han J Y, Kwon Y S, Yang D C, et al. Expression and RNA interferenceinduced silencing of the dammarenediol synthase gene in Panax ginseng. Plant Cell Physiol, 2006, 47(12): 1653~1662
［14］	Kim M K, Lee B S, In J G, et al. Comparative analysis of expressed sequence tags (ESTs) of ginseng leaf. Plant Cell Rep, 2006, 25: 599~606
［15］	罗志勇, 陆秋恒, 刘水平,等. 人参植物皂苷生物合成相关新基因的筛选与鉴定. 生物化学与生物物理学报, 2003, 35(6): 554~560 Luo Z Y, Lu Q H, Liu S P, et al. Acta Biochimica et Biophysica Sinica, 2003,35(6): 554~560
［16］	刘水平, 罗志勇, 陈湘晖,等. 人参皂苷生物合成相关新基因GBR6的cDNA克隆及序列分析. 生命科学研究, 2004, 8(4): 351~354 Liu S P, Luo Z Y, Chen X H, et al. Life Science Research, 2004, 8(4): 351~354
［17］	赵寿经, 侯春喜, 梁彦龙,等. 人参皂苷合成相关βAS基因的克隆及其反义植物表达载体的建立. 中国生物工程杂志, 2008, 28(4): 74~77 Zhao S J, Hou C X, Liang Y L, et al. China Biotechnology, 2008, 28(4) : 74~77
［18］	杨鹤, 郜玉钢, 李瑛,等. 人参皂苷等萜类化合物生物合成途径及HMGR的研究进展. 中国生物工程杂志, 2008, 28(10): 130~135 Yang H, Gao Y G, Li Y, et al. China Biotechnology, 2008, 28(10): 130~135
［19］	Jayvardhan Pandit D E D, Gayle K Schulte. Crystal structure of human squalene synthase.J Biol Chem, 2000, 275(39): 30610~30617
［20］	Uchida H, Yamashita H, Kajikawa M, et al. Cloning and characterization of a squalene synthase gene from a petroleum plant, Euphorbia tirucalli L. Planta, 2009,229(6):1243~1252
［21］	Do R K R, Gaudet D. Squalene synthase: a critical enzyme in the cholesterol biosynthesis pathway. Clin Genet, 2009, 75: 19~29
［22］	Devarenne T P, Ghosh A, Chappell J. Regulation of squalene synthase, a key enzyme of sterol biosynthesis, in tobacco. Plant Physiol, 2002, 129: 1095~1106
［23］	Massaki Shibuya H Z, Aki Endo. Two branches of the lupeol synthase gene in the molecular evolution of plant oxidosqualene cyclases. Eur J Biochem, 1999, 266: 302~307
［24］	Ormaetxe I I, Haralampidis K, Papadopoulou K, et al. Molecular cloning and characterization of triterpene synthases from Medicago truncatula and Lotus japonicus. Plant Mol Biol, 2003, 51: 731~743
［25］	Mohammad Basyuni H O, Etsuko Tsujimoto. Cloning and functional expression of cycloartenol synthases from Mangrove species Rhizophora stylosa Griff. and Kandelia candel(L.) Druce. Biosci. Biotechnol. Biochem., 2007, 71(7): 1788~1792
［26］	Muller T H, Schaller H, Benveniste P. Molecular cloning and expression in yeast of 2,3-oxidosqualene triterpene cyclases from Arabidopsis thaliana. Plant Mol Biol, 2001, 45: 75~92
［27］	Hiroaki Hayashi P H, Ara Kirakosyan. Cloning and characterization of a cDNA encoding β-amyrin synthase involved in glycyrrhizin and soyasaponin biosyntheses in licorice.Biol Pharm Bull, 2001, 24(8): 912~916
［28］	Masayo Morita M S, Tetsuo Kushiro. Molecular cloning and functional expression of triterpene synthases from pea(Pisum sativum).Eur J Biochem, 2000, 267: 3453~3460
［29］	Qi X, Bakht S, Leggett M, et al. A gene cluster for secondary metabolism in oat implications for the evolution of metabolic diversity in plants. PNAS, 2004, 101: 8233~8238
［30］	Shibuya M, Katsube Y, Otsuka M, et al. Identification of a product specific b-amyrin synthase from Arabidopsis thaliana. Plant Physiol Bioch, 2009, 47: 26~30
［31］	Shibuya M, Hoshino M, Katsude Y, et al. Identification of β-amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay. FEBS J, 2006, 273: 948~959
［32］	Jung J D,Hahm Y,Hur C G,et al. Discovery of genes for ginsenoside biosynthesis by analysis of ginseng expressed sequence tags. Plant Cell Rep, 2003, 22: 224~230
［33］	Lahoucine Achnine D V H, Mohamed A Farag, Lloyd W Sumner,et al. Genomics-based selection and functional characterization of triterpene glycosyltransferases from the model legume Medicago truncatula. The Plant Journal, 2005, 41: 875~887
［34］	Meesapyodsuk D, Balsevich J, Reed D W, et al. Saponin biosynthesis in Saponaria vaccaria. cDNAs encoding amyrin synthase and a triterpene carboxylic acid glucosyltransferase. Plant Physiol, 2006, 143: 959~969
［35］	王勇波，刘忠，赵爱华，等. 功能基因组学方法在药用植物次生代谢物研究中的应用. 中国中药杂志, 2009, 34(1): 6~10 Wan Y B, Liu Z, Zhao A H, et al. China Journal of Chinese Materia Medica, 2009, 34(1): 6~10
［36］	潘夕春，孙敏，张磊，等. RNA干扰及其在药用植物代谢工程中的应用. 中草药, 2005, 36(9): 1281~1284 Pan X C, Sun M, Zhang L, et al. Chinese Traditional and Herbal Drugs, 2005, 36(9): 1281~1284
［37］	Engels B, Dahm P, Jennewein S. Metabolic engineering of taxadiene biosynthesis in yeast as a first ste Ptowards Taxol (Paclitaxel) production. Metabolic Engineering, 2008, 10: 201~206
［38］	DaeKyun Ro,Mario Ouellet E M P. Metabolic engineering for plant natural product biosynthesis in microbes. Nature, 2006, 440: 940~943

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