Generic placeholder image

Current Pharmaceutical Biotechnology

Editor-in-Chief

ISSN (Print): 1389-2010
ISSN (Online): 1873-4316

Review Article

Ginseng Omics for Ginsenoside Biosynthesis

Author(s): Xianmei Yin, Haoyu Hu, Xiaofeng Shen, Xiangyan Li, Jin Pei* and Jiang Xu*

Volume 22, Issue 5, 2021

Published on: 07 August, 2020

Page: [570 - 578] Pages: 9

DOI: 10.2174/1389201021666200807113723

Price: $65

Abstract

Ginseng, also known as the king of herbs, has been regarded as an important traditional medicine for several millennia. Ginsenosides, a group of triterpenoid saponins, have been characterized as bioactive compounds of ginseng. The complexity of ginsenosides hindered ginseng research and development both in cultivation and clinical research. Therefore, deciphering the ginsenoside biosynthesis pathway has been a focus of interest for researchers worldwide. The new emergence of biological research tools consisting of omics and bioinformatic tools or computational biology tools are the research trend in the new century. Ginseng is one of the main subjects analyzed using these new quantification tools, including tools of genomics, transcriptomics, and proteomics. Here, we review the current progress of ginseng omics research and provide results for the ginsenoside biosynthesis pathway. Organization and expression of the entire pathway, including the upstream MVA pathway, the cyclization of ginsenoside precursors, and the glycosylation process, are illustrated. Regulatory gene families such as transcriptional factors and transporters are also discussed in this review.

Keywords: Panax ginseng, ginsenoside, genomics, transcriptomics, proteomics, metabolomics.

Graphical Abstract
[1]
Hemmerly, T.E. A ginseng farm in Lawrence County, Tennessee. Econ. Bot., 1977, 31, 160-162.
[http://dx.doi.org/10.1007/BF02866586]
[2]
Leung, K.W.; Wong, A.S. Pharmacology of ginsenosides: a literature review. Chin. Med., 2010, 5, 20.
[http://dx.doi.org/10.1186/1749-8546-5-20] [PMID: 20537195]
[3]
Liu, C.X.; Xiao, P.G. Recent advances on ginseng research in China. J. Ethnopharmacol., 1992, 36(1), 27-38.
[http://dx.doi.org/10.1016/0378-8741(92)90057-X] [PMID: 1501490]
[4]
Goldstein, B. Ginseng: its history, dispersion, and folk tradition. Am J Chin Med (Gard City N Y), 1975, 3(3), 223-234.
[http://dx.doi.org/10.1142/S0192415X75000244] [PMID: 1103611]
[5]
Gillis, C.N. Panax ginseng pharmacology: a nitric oxide link? Biochem. Pharmacol., 1997, 54(1), 1-8.
[http://dx.doi.org/10.1016/S0006-2952(97)00193-7] [PMID: 9296344]
[6]
Coon, J.T.; Ernst, E. Panax ginseng: a systematic review of adverse effects and drug interactions. Drug Saf., 2002, 25(5), 323-344.
[http://dx.doi.org/10.2165/00002018-200225050-00003] [PMID: 12020172]
[7]
Zhang, Y.C.; Li, G.; Jiang, C.; Yang, B.; Yang, H.J.; Xu, H.Y.; Huang, L.Q. Tissue-specific distribution of ginsenosides in different aged ginseng and antioxidant activity of ginseng leaf. Molecules, 2014, 19(11), 17381-17399.
[http://dx.doi.org/10.3390/molecules191117381] [PMID: 25353387]
[8]
Fukuda, N.; Shan, S.; Tanaka, H.; Shoyama, Y. New staining methodology: eastern blotting for glycosides in the field of Kampo medicines. J. Nat. Med., 2005, 60, 21-27.
[http://dx.doi.org/10.1007/s11418-005-0005-3]
[9]
Taira, S.; Ikeda, R.; Yokota, N.; Osaka, I.; Sakamoto, M.; Kato, M.; Sahashi, Y. Mass spectrometric imaging of ginsenosides localization in Panax ginseng root. Am. J. Chin. Med., 2010, 38(3), 485-493.
[http://dx.doi.org/10.1142/S0192415X10008007] [PMID: 20503467]
[10]
Yokota, S.; Onohara, Y.; Shoyama, Y. Immunofluorescence and immunoelectron microscopic localization of medicinal substance, Rb1, in several plant parts of Panax ginseng. Curr. Drug Discov. Technol., 2011, 8(1), 51-59.
[http://dx.doi.org/10.2174/157016311794519938] [PMID: 21143133]
[11]
Christensen, L.P.; Jensen, M.; Kidmose, U. Simultaneous determination of ginsenosides and polyacetylenes in American ginseng root (Panax quinquefolium L.) by high-performance liquid chromatography. J. Agric. Food Chem., 2006, 54(24), 8995-9003.
[http://dx.doi.org/10.1021/jf062068p] [PMID: 17117783]
[12]
Tani, T.; Kubo, M.; Katsuki, T.; Higashino, M.; Hayashi, T.; Arichi, S.; Histochemistry, I.I. Ginsenosides in ginseng (Panax ginseng, root). J. Nat. Prod., 1981, 44, 401-407.
[http://dx.doi.org/10.1021/np50016a002]
[13]
Augustin, J.M.; Kuzina, V.; Andersen, S.B.; Bak, S. Molecular activities, biosynthesis and evolution of triterpenoid saponins. Phytochemistry, 2011, 72(6), 435-457.
[http://dx.doi.org/10.1016/j.phytochem.2011.01.015] [PMID: 21333312]
[14]
Wu, W.; Lu, Z.; Teng, Y.; Guo, Y.; Liu, S. Structural Characterization of Ginsenosides from Flower Buds of Panax ginseng by RRLC-Q-TOF MS. J. Chromatogr. Sci., 2016, 54(2), 136-143.
[PMID: 26270079]
[15]
Wang, H.; Zhang, C.; Zuo, T.; Li, W.; Jia, L.; Wang, X.; Qian, Y.; Guo, D.; Yang, W. In-depth profiling, characterization, and comparison of the ginsenosides among three different parts (the root, stem leaf, and flower bud) of Panax quinquefolius L. by ultra-high performance liquid chromatography/quadrupole-Orbitrap mass spectrometry. Anal. Bioanal. Chem., 2019, 411(29), 7817-7829.
[http://dx.doi.org/10.1007/s00216-019-02180-8] [PMID: 31729585]
[16]
Jia, L.; Zuo, T.; Zhang, C.; Li, W.; Wang, H.; Hu, Y.; Wang, X.; Qian, Y.; Yang, W.; Yu, H. Simultaneous profiling and holistic comparison of the metabolomes among the flower buds of Panax ginseng, Panax quinquefolius, and Panax notoginseng by UHPLC/IM-QTOF-HDMSE-based metabolomics analysis. Molecules, 2019, 24(11)E2188
[http://dx.doi.org/10.3390/molecules24112188] [PMID: 31212627]
[17]
Zhang, C.; Zuo, T.; Wang, X.; Wang, H.; Hu, Y.; Li, Z.; Li, W.; Jia, L.; Qian, Y.; Yang, W.; Yu, H. Integration of Data-Dependent Acquisition (DDA) and Data-Independent High-Definition MSE (HDMSE) for the Comprehensive Profiling and Characterization of Multicomponents from Panax japonicus by UHPLC/IM-QTOF-MS. Molecules, 2019, 24(15)E2708
[http://dx.doi.org/10.3390/molecules24152708] [PMID: 31349632]
[18]
Shi, X.; Yang, W.; Huang, Y.; Hou, J.; Qiu, S.; Yao, C.; Feng, Z.; Wei, W.; Wu, W.; Guo, D.; Changliang, Y. Direct screening of malonylginsenosides from nine Ginseng extracts by an untargeted profiling strategy incorporating in-source collision-induced dissociation, mass tag, and neutral loss scan on a hybrid linear ion-trap/Orbitrap mass spectrometer coupled to ultra-high performance liquid chromatography. J. Chromatogr. A, 2018, 1571, 213-222.
[http://dx.doi.org/10.1016/j.chroma.2018.08.026] [PMID: 30146372]
[19]
Xu, J.; Chu, Y.; Liao, B.; Xiao, S.; Yin, Q.; Bai, R.; Su, H.; Dong, L.; Li, X.; Qian, J.; Zhang, J.; Zhang, Y.; Zhang, X.; Wu, M.; Zhang, J.; Li, G.; Zhang, L.; Chang, Z.; Zhang, Y.; Jia, Z.; Liu, Z.; Afreh, D.; Nahurira, R.; Zhang, L.; Cheng, R.; Zhu, Y.; Zhu, G.; Rao, W.; Zhou, C.; Qiao, L.; Huang, Z.; Cheng, Y.C.; Chen, S. Panax ginseng genome examination for ginsenoside biosynthesis. Gigascience, 2017, 6(11), 1-15.
[http://dx.doi.org/10.1093/gigascience/gix093] [PMID: 29048480]
[20]
Kim, N.H.; Jayakodi, M.; Lee, S.C.; Choi, B.S.; Jang, W.; Lee, J.; Kim, H.H.; Waminal, N.E.; Lakshmanan, M.; van Nguyen, B.; Lee, Y.S.; Park, H.S.; Koo, H.J.; Park, J.Y.; Perumal, S.; Joh, H.J.; Lee, H.; Kim, J.; Kim, I.S.; Kim, K.; Koduru, L.; Kang, K.B.; Sung, S.H.; Yu, Y.; Park, D.S.; Choi, D.; Seo, E.; Kim, S.; Kim, Y.C.; Hyun, D.Y.; Park, Y.I.; Kim, C.; Lee, T.H.; Kim, H.U.; Soh, M.S.; Lee, Y. In, J.G.; Kim, H.S.; Kim, Y.M.; Yang, D.C.; Wing, R.A.; Lee, D.Y.; Paterson, A.H.; Yang, T.J. Genome and evolution of the shade-requiring medicinal herb Panax ginseng. Plant Biotechnol. J., 2018, 16(11), 1904-1917.
[http://dx.doi.org/10.1111/pbi.12926] [PMID: 29604169]
[21]
Jayakodi, M.; Choi, B.S.; Lee, S.C.; Kim, N.H.; Park, J.Y.; Jang, W.; Lakshmanan, M.; Mohan, S.V.G.; Lee, D.Y.; Yang, T.J. Ginseng Genome Database: an open-access platform for genomics of Panax ginseng. BMC Plant Biol., 2018, 18(1), 62.
[http://dx.doi.org/10.1186/s12870-018-1282-9] [PMID: 29649979]
[22]
Chu, Y.; Xu, R.; Su, H.; Liao, B.S.; Wu, M.L.; Xu, J. Genome-wide analysis of NBS-LRR-encoding gene in Panax ginseng. Scientia Sinica (Vitae), 2018, 48, 423-435.
[http://dx.doi.org/10.1360/N052017-00197]
[23]
Chu, Y.; Xiao, S.; Su, H.; Liao, B.; Zhang, J.; Xu, J.; Chen, S. Genome-wide characterization and analysis of bHLH transcription factors in Panax ginseng. Acta Pharm. Sin. B, 2018, 8(4), 666-677.
[http://dx.doi.org/10.1016/j.apsb.2018.04.004] [PMID: 30109190]
[24]
Guo, H.; Zhang, Y.; Wang, Z.; Lin, L.; Cui, M.; Long, Y.; Xing, Z. Genome-wide identification of WRKY transcription factors in the Asteranae. Plants (Basel), 2019, 8(10), 393.
[http://dx.doi.org/10.3390/plants8100393] [PMID: 31581604]
[25]
Lee, M.H.; Jeong, J.H.; Seo, J.W.; Shin, C.G.; Kim, Y.S.; In, J.G.; Yang, D.C.; Yi, J.S.; Choi, Y.E. Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol., 2004, 45(8), 976-984.
[http://dx.doi.org/10.1093/pcp/pch126] [PMID: 15356323]
[26]
Han, J.Y.; In, J.G.; Kwon, Y.S.; Choi, Y.E. Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epoxidase gene in Panax ginseng. Phytochemistry, 2010, 71(1), 36-46.
[http://dx.doi.org/10.1016/j.phytochem.2009.09.031] [PMID: 19857882]
[27]
Phillips, D.R.; Rasbery, J.M.; Bartel, B.; Matsuda, S.P. Biosynthetic diversity in plant triterpene cyclization. Curr. Opin. Plant Biol., 2006, 9(3), 305-314.
[http://dx.doi.org/10.1016/j.pbi.2006.03.004] [PMID: 16581287]
[28]
Han, J.Y.; Kim, H.J.; Kwon, Y.S.; Choi, Y.E. The Cyt P450 enzyme CYP716A47 catalyzes the formation of protopanaxadiol from dammarenediol-II during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol., 2011, 52(12), 2062-2073.
[http://dx.doi.org/10.1093/pcp/pcr150] [PMID: 22039120]
[29]
Han, J.Y.; Hwang, H.S.; Choi, S.W.; Kim, H.J.; Choi, Y.E. Cytochrome P450 CYP716A53v2 catalyzes the formation of protopanaxatriol from protopanaxadiol during ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol., 2012, 53(9), 1535-1545.
[http://dx.doi.org/10.1093/pcp/pcs106] [PMID: 22875608]
[30]
Han, J.Y.; Kim, M.J.; Ban, Y.W.; Hwang, H.S.; Choi, Y.E. The involvement of β-amyrin 28-oxidase (CYP716A52v2) in oleanane-type ginsenoside biosynthesis in Panax ginseng. Plant Cell Physiol., 2013, 54(12), 2034-2046.
[http://dx.doi.org/10.1093/pcp/pct141] [PMID: 24092881]
[31]
Jenner, H.; Townsend, B.; Osbourn, A. Unravelling triterpene glycoside synthesis in plants: phytochemistry and functional genomics join forces. Planta, 2005, 220(4), 503-506.
[http://dx.doi.org/10.1007/s00425-004-1434-z] [PMID: 15703926]
[32]
Liang, Y.; Zhao, S. Progress in understanding of ginsenoside biosynthesis. Plant Biol (Stuttg), 2008, 10(4), 415-421.
[http://dx.doi.org/10.1111/j.1438-8677.2008.00064.x] [PMID: 18557901]
[33]
Thimmappa, R.; Geisler, K.; Louveau, T.; O’Maille, P.; Osbourn, A. Triterpene biosynthesis in plants. Annu. Rev. Plant Biol., 2014, 65, 225-257.
[http://dx.doi.org/10.1146/annurev-arplant-050312-120229] [PMID: 24498976]
[34]
Yan, X.; Fan, Y.; Wei, W.; Wang, P.; Liu, Q.; Wei, Y.; Zhang, L.; Zhao, G.; Yue, J.; Zhou, Z. Production of bioactive ginsenoside compound K in metabolically engineered yeast. Cell Res., 2014, 24(6), 770-773.
[http://dx.doi.org/10.1038/cr.2014.28] [PMID: 24603359]
[35]
Jung, S.C.; Kim, W.; Park, S.C.; Jeong, J.; Park, M.K.; Lim, S.; Lee, Y. Im, W.T.; Lee, J.H.; Choi, G.; Kim, S.C. Two ginseng UDP-glycosyltransferases synthesize ginsenoside Rg3 and Rd. Plant Cell Physiol., 2014, 55(12), 2177-2188.
[http://dx.doi.org/10.1093/pcp/pcu147] [PMID: 25320211]
[36]
Wei, W.; Wang, P.; Wei, Y.; Liu, Q.; Yang, C.; Zhao, G.; Yue, J.; Yan, X.; Zhou, Z. Characterization of Panax ginseng UDP-glycosyltransferases catalyzing protopanaxatriol and biosyntheses of bioactive ginsenosides F1 and Rh1 in metabolically engineered yeasts. Mol. Plant, 2015, 8(9), 1412-1424.
[http://dx.doi.org/10.1016/j.molp.2015.05.010] [PMID: 26032089]
[37]
Li, C.; Zhu, Y.; Guo, X.; Sun, C.; Luo, H.; Song, J.; Li, Y.; Wang, L.; Qian, J.; Chen, S. Transcriptome analysis reveals ginsenosides biosynthetic genes, microRNAs and simple sequence repeats in Panax ginseng C. A. Meyer. BMC Genomics, 2013, 14, 245.
[http://dx.doi.org/10.1186/1471-2164-14-245] [PMID: 23577925]
[38]
Chen, S.; Luo, H.; Li, Y.; Sun, Y.; Wu, Q.; Niu, Y.; Song, J.; Lv, A.; Zhu, Y.; Sun, C.; Steinmetz, A.; Qian, Z. 454 EST analysis detects genes putatively involved in ginsenoside biosynthesis in Panax ginseng. Plant Cell Rep., 2011, 30(9), 1593-1601.
[http://dx.doi.org/10.1007/s00299-011-1070-6] [PMID: 21484331]
[39]
Wang, K.; Jiang, S.; Sun, C.; Lin, Y.; Yin, R.; Wang, Y.; Zhang, M. The Spatial and Temporal Transcriptomic Landscapes of Ginseng, Panax ginseng C. A. Meyer. Sci. Rep., 2015, 5, 18283.
[http://dx.doi.org/10.1038/srep18283] [PMID: 26655864]
[40]
Jayakodi, M.; Lee, S.C.; Park, H.S.; Jang, W.; Lee, Y.S.; Choi, B.S.; Nah, G.J.; Kim, D.S.; Natesan, S.; Sun, C.; Yang, T.J. Transcriptome profiling and comparative analysis of Panax ginseng adventitious roots. J. Ginseng Res., 2014, 38(4), 278-288.
[http://dx.doi.org/10.1016/j.jgr.2014.05.008] [PMID: 25379008]
[41]
Kim, S.W.; Lee, S.H.; Min, C.W.; Jo, I.H.; Bang, K.H.; Hyun, D.Y.; Agrawal, G.K. Rakwal, R.; Zargar, S.M.; Gupta, R. Kim, S.T. Ginseng (Panax sp.) proteomics: an update. Appl. Biol. Chem., 2017, 60, 311-320.
[http://dx.doi.org/10.1007/s13765-017-0283-y]
[42]
Ma, R.; Sun, L.; Chen, X.; Jiang, R.; Sun, H.; Zhao, D. Proteomic changes in different growth periods of ginseng roots. Plant Physiol. Biochem., 2013, 67, 20-32.
[http://dx.doi.org/10.1016/j.plaphy.2013.02.023] [PMID: 23537955]
[43]
Nam, M.H.; Kim, S.I.; Liu, J.R.; Yang, D.C.; Lim, Y.P.; Kwon, K.H.; Yoo, J.S.; Park, Y.M. Proteomic analysis of Korean ginseng (Panax ginseng C.A. Meyer). J. Chromatogr. B Analyt. Technol. Biomed. Life Sci., 2005, 815(1-2), 147-155.
[http://dx.doi.org/10.1016/j.jchromb.2004.10.063] [PMID: 15652805]
[44]
Colzani, M.; Altomare, A.; Caliendo, M.; Aldini, G.; Righetti, P.G.; Fasoli, E. The secrets of Oriental panacea: Panax ginseng. J. Proteomics, 2016, 130, 150-159.
[http://dx.doi.org/10.1016/j.jprot.2015.09.023] [PMID: 26388432]
[45]
Yang, D.C.; Kim, S.I.; Kim, S.J.; Jo, I.H.; Kim, S.T. Purification of crude protein mixture from Panax ginseng and hairy root for proteome analysis. Korean J. Plant Tissue Culture, 2001, 28, 347-351.
[46]
Ye, X.; Zhao, N.; Yu, X.; Han, X.; Gao, H.; Zhang, X. Extensive characterization of peptides from Panax ginseng C. A. Meyer using mass spectrometric approach. Proteomics, 2016, 16(21), 2788-2791.
[http://dx.doi.org/10.1002/pmic.201600183] [PMID: 27604500]
[47]
Ma, R.; Sun, L.; Chen, X.; Mei, B.; Chang, G.; Wang, M.; Zhao, D. Proteomic analyses provide novel insights into plant growth and ginsenoside biosynthesis in forest cultivated Panax ginseng (F. Ginseng). Front. Plant Sci., 2016, 7, 1.
[http://dx.doi.org/10.3389/fpls.2016.00001] [PMID: 26858731]
[48]
Lum, J.H.K.; Fung, K.L.; Cheung, P.Y.; Wong, M.S.; Lee, C.H.; Kwok, F.S.L.; Leung, M.C.P.; Hui, P.K.; Lo, S.C.L. Proteome of Oriental ginseng Panax ginseng C. A. Meyer and the potential to use it as an identification tool. Proteomics, 2002, 2(9), 1123-1130.
[http://dx.doi.org/10.1002/1615-9861(200209)2:9<1123:AID-PROT1123>3.0.CO;2-S] [PMID: 12362331]
[49]
Vergara, F.; Rymen, B.; Kuwahara, A.; Sawada, Y.; Sato, M.; Hirai, M.Y. Autopolyploidization, geographic origin, and metabolome evolution in Arabidopsis thaliana. Am. J. Bot., 2017, 104(6), 905-914.
[http://dx.doi.org/10.3732/ajb.1600419] [PMID: 28626037]
[50]
Wang, W.; Li, Y.; Dang, P.; Zhao, S.; Lai, D.; Zhou, L. Rice Secondary Metabolites: Structures, Roles, Biosynthesis, and Metabolic Regulation. Molecules, 2018, 23(12), 3098.
[http://dx.doi.org/10.3390/molecules23123098] [PMID: 30486426]

Rights & Permissions Print Cite
© 2024 Bentham Science Publishers | Privacy Policy