Journal of Plant Biotechnology

The Korean Society of Plant Biotechnology (한국식물생명공학회)
권호 표지
DOI QR코드

DOI QR Code

Metabolic engineering for production of ginsenosides in Panax ginseng

인삼 사포닌 생산을 위한 대사공학

  • Kim, Tae-Dong (Division of Forest Resources, College of Forest an Environmental Sciences, Kangwon National University) ;
  • Kim, Yun-Soo (Division of Forest Resources, College of Forest an Environmental Sciences, Kangwon National University) ;
  • Han, Jung-Yeon (Division of Forest Resources, College of Forest an Environmental Sciences, Kangwon National University) ;
  • Lim, Soon (Division of Forest Resources, College of Forest an Environmental Sciences, Kangwon National University) ;
  • Choi, Yong-Eui (Division of Forest Resources, College of Forest an Environmental Sciences, Kangwon National University)
  • 김태동 (강원대학교 산림환경과학대학 산림자원학부) ;
  • 김윤수 (강원대학교 산림환경과학대학 산림자원학부) ;
  • 한정연 (강원대학교 산림환경과학대학 산림자원학부) ;
  • 임순 (강원대학교 산림환경과학대학 산림자원학부) ;
  • 최용의 (강원대학교 산림환경과학대학 산림자원학부)
  • Published : 2009.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Panax ginseng roots produce triterpene saponins called ginsenosides, which are high value secondary metabolites and has been used as drugs, detergents, sweeteners, and cosmetics. In the recent years plant cell, tissue and organ cultures have developed as important alternative sources for the saponin production in Panax ginseng. Adventitious roots and hairy roots have been successfully induced and cultured for the improvement of saponin contents. Genetic and metabolic engineering to regulate saponin biosynthesis in P. ginseng might be important way to improve the medicinal values of P. ginseng. Here we introduced the protocol of genetic transformation and recent progress of functional characterization of genes involved in saponin biosynthesis in P. ginseng.

Keywords

References

  1. Abe I, Rohmer M, Prestwich GD (1993) Enzymatic cyclization of squalene and oxidosqualene to sterols and triterpenes. Chem Rev 93:2189-2206 https://doi.org/10.1021/cr00022a009
  2. Agostini E, de Forchetti SM, Tigier HA (1997) Production of peroxidases by hairy roots of Brassica napus. Plant Cell Tiss Organ Cult 47:177-182 https://doi.org/10.1007/BF02318955
  3. Arya S, Liu JR, Eriksson T (1991) Plant regeneration from protoplasts of Panax ginseng (C.A. Meyer) through somatic embryogenesis. Plant Cell Rep 10:277-281 https://doi.org/10.1007/BF00193141
  4. Butenco RG, Brushwitzky IV, Slepyan LI (1968) Organogenesis and somatic embryogenesis in the tissue culture of Panax ginseng C. A. Meyer. Bot Zh 7:906-913
  5. Choi YE, Soh WY (1997) Enhanced somatic single embryo formation by plasmolyzing pretreatment from cultured ginseng cotyledons. Plant Sci 130:197-206 https://doi.org/10.1016/S0168-9452(97)00217-3
  6. Choi YE, Yang DC, Choi KT (1998a) Induction of somatic embryos by macrosalt stress from mature zygotic embryos of Panax ginseng. Plant Cell Tissue Organ Cult 52:177-182 https://doi.org/10.1023/A:1005971712628
  7. Choi YE, Yang DC, Park JC, Soh WY, Choi KT (1998b) Regenerative ability of somatic single and multiple embryos from cotyledons of Korean ginseng on hormone-free medium. Plant Cell Rep 17:544-551 https://doi.org/10.1007/s002990050439
  8. Choi YE, Yang DC, Yoon ES, Choi KT (1998c) Plant regeneration via adventitious bud formation from cotyledon explants of Panax ginseng C.A. Meyer. Plant Cell Rep 17:731-736 https://doi.org/10.1007/s002990050474
  9. Choi YE, Yang DC, Yoon ES, Choi KT (1999a) High efficiency plant production via direct somatic single embryogenesis from pre-plasmolysed cotyledons of Panax ginseng and possible dormancy of somatic embryos. Plant Cell Rep 18: 493-499 https://doi.org/10.1007/s002990050610
  10. Choi YE, Yang DC, Yoon ES, Choi KT (1999b) Plant regeneration via direct embryo axis-like shoot and root formation from excised cotyledon explants of ginseng seedlings. In Vitro Cell Dev Biol Plant 35:210-213 https://doi.org/10.1007/s11627-999-0079-9
  11. Chang WC, Hsing YI (1980) Plant regeneration through somatic embryogenesis in root-derived callus of ginseng (Panax ginseng C. A. Meyer). Theor Appl Genet 57:133-135 https://doi.org/10.1007/BF00253888
  12. Chilton MD, Tepfer D, Petit A, David C, Casse-Delbart F, Tempe J (1982) Agrobacterium rhizogenes inserts T-DNA into the genomes of host plant root cells. Nature 295:432-434 https://doi.org/10.1038/295432a0
  13. Cui JF, Eneroth P, Bruhn JC (1999) Gynostemma pentaphyllum: identification of major sapogenins and differentiation from Panax species. Eur J Pharm Sci 8:187-191 https://doi.org/10.1016/S0928-0987(99)00013-5
  14. Choi SM, Son SH, Kwon OW, Seon JH, Paek KY (2000) Pilot-scale culture of adventitious roots of ginseng in a bioreactor system. Plant Cell Tissue Organ Cult 62:187-193 https://doi.org/10.1023/A:1006412203197
  15. Choi DW, Jung JD, Ha YI, Park HW, In DS, Chung HJ, Liu JR (2005) Analysis of transcripts in methyl jasmonate-treated ginseng hairy roots to identify genes involved in the biosynthesis of ginsenosides and other secondary metabolites.Plant Cell Rep 23:557-566 https://doi.org/10.1007/s00299-004-0845-4
  16. Chen WP, Punja ZK (2002) Agrobacterium-mediated transformation of American ginseng with a rice chitnase gene. Plant Cell Rep 20:1039-1045 https://doi.org/10.1007/s00299-002-0446-z
  17. Choi YE, Yang DC, Kusano T, Sano H (2001) Rapid and efficient Agrobacterium-mediated genetic transformation by plasmolyzing pretreatment of cotyledons in Panax ginseng. Plant Cell Rep 20:616-621 https://doi.org/10.1007/s002990100377
  18. Choi YE, Jeong JH, In JK, Yang DC (2003) Production of herbicide-resistant transgenic Panax ginseng through the introduction of phosphinotricin acetyl transferase gene and successful soil transfer. Plant Cell Rep 21:563-56
  19. Choi M, Shin GJ, Choi GP, Do JH, Kim JD (2003) Synergistic effects of extracts from Korean red ginseng, saururus chinensis (Lour.) Baill and Rubus coreanus Miq on antioxidative activites in rats. Korean J Medical Crop Sci 14:27-30
  20. Coleman CI, Hebert JH, Reddy P (2003) The effects of Panax ginseng on quality of life. J Clin Pharm Ther 28:5-15 https://doi.org/10.1046/j.1365-2710.2003.00467.x
  21. Dey L, Xie JT, Wang A, Wu J, Maleckar SA, Yuan CS (2003) Anti-hyperglycemic effects of ginseng: comparison between root and berry. Phytomedicine 10:600-605 https://doi.org/10.1078/094471103322331908
  22. Ellis JM, Reddy P (2002) Effects of Panax ginseng on quality of life. Ann Pharmacother 36:375-379 https://doi.org/10.1345/aph.1A245
  23. Furuya T, Yoshikawa T, Ishii T, Kajii K (1983) Regulation of saponin production in callus cultures of Panax ginseng. Plant Med 47:200-204 https://doi.org/10.1055/s-2007-969985
  24. Furuya T, Yoshikawa T, Orihara Y, Oda H (1984) Studies of the culture conditions for Panax ginseng cells in jar fermentors. J Nat Prod 47:70-75 https://doi.org/10.1021/np50031a008
  25. Giri A, Narasu ML (2000) Transgenic hairy roots: recent trends and applications. Biotechnol Adv 18:1-22 https://doi.org/10.1016/S0734-9750(99)00016-6
  26. Han BH, Park MH, Wee JJ (1985) Studies on antioxidant components of Korean ginseng (V). The mechanism of antioxidant activity of maltol and phenolic acid. Korean Biochem J 18:337-340
  27. Han JY, Choi YE (2009) Rapid induction of Agrobacterium tumefaciens-mediated transgenic roots directly from adventitious roots in Panax ginseng. Plant Cell Tiss Organ Cult 96:143-149 https://doi.org/10.1007/s11240-008-9470-1
  28. Han JY, Kwon YS, Yang DC, Jung YR, Choi YE (2006) Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng. Plant Cell Physiol 47:1653-1662 https://doi.org/10.1093/pcp/pcl032
  29. Han JY, In JG, Kwon YS, Choi YE (2010) Regulation of ginsenoside and phytosterol biosynthesis by RNA interferences of squalene epoxidase gene in Panax ginseng. Phytochemistry 71:36-46 https://doi.org/10.1016/j.phytochem.2009.09.031
  30. Hahn EJ, Kim YS, Yu KW, Jeong CS, Paek KY (2004) Adventitious root cultures of Panax ginseng C.A. Meyer and ginsenoside production through large-scale bioreactor system. J Plant Biotech 5:1-6
  31. Han JY, Kwon YS, Yang DC, Jung YR, Choi YE (2006) Expression and RNA interference-induced silencing of the dammarenediol synthase gene in Panax ginseng. Plant Cell Physiol 47:1653-1662 https://doi.org/10.1093/pcp/pcl032
  32. Haralampidis K, Trojanowska M, Osbourn AE (2001) Biosynthesis of triterpenoid saponin in plants. Adv Biochem Eng Biotechnol 75:31-49 https://doi.org/10.1007/3-540-44604-4_2
  33. Hoffmann F, Hoffmann-Tsay SS (1994) Growth regulator-free plant regeneration and habituated cell suspensions from carrot protoplasts. Differentiation 57:1-5 https://doi.org/10.1046/j.1432-0436.1994.5710001.x
  34. Hostettmann K, Marston A (1995) Chemistry and pharmacology of natrual products: Saponins. Cambridge Univ Press, NY
  35. Hwang B, Ko KM, Hwang SJ, Kang YH (1991) Production of saponin by hairy root cultures of ginseng (Panax ginseng C.A. Meyer) transformed with A. rhizogenes. Kor J Bot 34:289-296
  36. Hwang WI, Oh S K (1996) Effects of petroleum extract of ginseng root on some enzyme activity in human colon cancer cell. Korean J Ginseng Res 10:27-35
  37. Janick J (2007) The origins of horticultural technology and science. Acta Hort 759:41-60
  38. Jeong GT, Park DH, Ryu HW, Hwang B, Woo JC, Doman KF, Kim SW (2005) Production of antioxidant compounds by culture of Panax ginseng C.A. Meyer hairy roots I. Enhanced production of secondary metabolite in hairy root cultures by elicitation. Appl Biochem Biotechnol 121:1147-115 https://doi.org/10.1385/ABAB:124:1-3:1147
  39. Kwon WS, Lee MK, Choi KT (2000) Breeding process and characteristics of Yunpoong, a new variety of Panax ginseng C.A. Meyer. J Ginseng Res 24:1226-8453
  40. Kiefer D, Pantuso T (2003) Panax ginseng. Am Fam Physician 68:1539-1542
  41. Kevers C, Jacques P, Thonart P, Gaspar T (1999) In vitro root cultures of Panax ginseng and P. quinquefolium. Plant Growth Regul 27:173-178 https://doi.org/10.1023/A:1006266413919
  42. Kim YS, Hahn EJ, Murthy HN, Paek KY (2004) Adventitious root growth and ginsenoside accumulation in Panax ginseng cultures as affected by methyl jasmonate. Biotechnol Lett 26:1619-1622 https://doi.org/10.1007/s10529-004-3183-2
  43. Kim YS, Hahn EJ, Paek KY (2005) Effects of aeration and sparger type on growth and ginsenoside accumulation in bioreactor cultures of ginseng adventitious root (Panax ginseng). Kor J Plant Biotech 32:111-116 https://doi.org/10.5010/JPB.2005.32.2.111
  44. Kushiro T, Ohno Y, Shibuya M, Ebizuka Y (1997) In vitro conversion of 2,3-oxidosqualene into dammarenediol by Panax ginseng microsome. Biol Pharm Bull 20:292-294 https://doi.org/10.1248/bpb.20.292
  45. Kuzuyama T (2002) Mevalonate and nonmevalonate pathways for the biosynthesis of isoprene units. Biosci Biotechnol Biochem 66:1619-1627 https://doi.org/10.1271/bbb.66.1619
  46. Kushiro T, Shibuya M, Ebizuka Y (1998) $\beta$-Amyrin synthase: cloning of oxidosqualene cyclase that catalyzes the formation of the most popular triterpene among higher plants. Eur J Biochem 256:238-244 https://doi.org/10.1046/j.1432-1327.1998.2560238.x
  47. Ko KS, Heo IO, Ko JS, Lee WJ (1990) Ginsenoside production by hairy root cultures of Panax ginseng transformed with Agrobacterium rhizogenes. Kor J Biotechnol Bioeng 5:263-268
  48. Ko KM, Ahn JH, Hwang SJ, Kang YH, Hwang B (1993) Production of secondary metabolites from hairy root of Panax ginseng transformed by Agrobacterium rhizogenes. II. Improvement of saponin contents and mass cultures of ginseng hairy root. Korean J Plant Tissue Culture 20:41-46
  49. Kuribayashi T, Ohashi H (1971) Physiological and ecological studies in Panax ginseng. Ⅱ. Effects of various temperature and chemical control substances on the germination. Syoyakugaku Zasshi 25:95-101
  50. Lee MH, Jeong JH, Seo JW, Shin CG, Kim YS, In JG, Yang DC, Yi JS, Choi YE (2004) Enhanced triterpene and phytosterol biosynthesis in Panax ginseng overexpressing squalene synthase gene. Plant Cell Physiol 45:976-984 https://doi.org/10.1093/pcp/pch126
  51. Lee HS, Kim SW, Lee KW, Eriksson T, Liu JR (1995) Agrobacterium-mediated transformation of ginseng (Panax ginseng) and mitotic stability of the inserted $\beta$-glucuronidase gene in regenerants from isolated protoplasts. Plant Cell Rep 14:545-549 https://doi.org/10.1007/BF00231935
  52. Lee JS, Ko KM, Ahn JC, Bai DG, Park KY, Ko SR, Hwang B (1994) High yield saponin production by mass cultures of ginseng transformed tissue Ι. Induction, culture of transformed tissue and selection of high-saponin-producing clones in ginseng. Korean J Biotechnol Bioeng 9:157-164
  53. Lim S, Bae KH, Shin CG, Kim YY, Kim YS (2005) Increasement of secondary metabolites and antioxidative activity in Panax ginseng adventitious root by methyl jasmonate. Kor J Plant Biotech 32:225-231 https://doi.org/10.5010/JPB.2005.32.3.225
  54. Lin W, Anuratha CS, Datta K, Potrykus I, Muthukrishnan S, Datta SK (1995) Genetic engineering of rice for resistance to sheath blight. Bio/Technology 13:686-691 https://doi.org/10.1038/nbt0795-686
  55. Matsumoto T, Akihisa T, Soma S, Takido M, Takahashi S (1986) Composition of unsaponifiable lipid from seed oils of Panax ginseng and Panax quinquefolium. J Am Oil Chem Soc 63:544-546 https://doi.org/10.1007/BF02645749
  56. Nam MH, Kim SI, Liu JR, Yang DC, Lim YP, Kwon KH, Yoo JS, Park YM (2005) Proteomic analysis of Korean ginseng(Panax ginseng C.A. Meyer). J Chromatogra B 815:147-155 https://doi.org/10.1016/j.jchromb.2004.10.063
  57. Park CK, Jeon BS, Yang JW (2003) The chemical components of Korean ginseng. Food industry and Nutrition 8:10-24
  58. Ramsay G, Kumar A (1990) Transformation of Vicia faba cotyledon and stem tissues by Agrobacterium rhizogenes: Infectivity and cytological studies. J Exp Bot 41:841-847 https://doi.org/10.1093/jxb/41.7.841
  59. Shoyama Y, Kamura K, Nishioka I (1988) Somatic embryogenesis and clonal multiplication of Panax ginseng. Planta Med 54:155-156 https://doi.org/10.1055/s-2006-962376
  60. Shanks JV, Morgan J (1999) Plant 'hairy root' culture. Curr Opin Biotechnol 10:151-155 https://doi.org/10.1016/S0958-1669(99)80026-3
  61. Shibata S (2001) Chemistry and cancer preventing activities of ginseng saponins and some related triterpenoid compounds. J Kor Med Sci 16[Suppl]:S28-S37 https://doi.org/10.3346/jkms.2001.16.S.S28
  62. Shibuya M, Hoshino M, Katsube Y, Hayashi H, Kushiro T, Ebizuka Y (2006) Identification of β-Amyrin and sophoradiol 24-hydroxylase by expressed sequence tag mining and functional expression assay. FEBS J 273:948-959 https://doi.org/10.1111/j.1742-4658.2006.05120.x
  63. Tansakul P, Shibuya M, Kushiro T, Ebizuka Y (2006) Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Letters 580:5143-5149 https://doi.org/10.1016/j.febslet.2006.08.044
  64. Vogler BK, Pittler MH, Ernst E (1999) The efficacy of ginseng. A systematic review of randomized clinical trials. Eur J Clin Pharmacol 55:567-575 https://doi.org/10.1007/s002280050674
  65. Wang W, Zhong JJ (2002) Manipulation of ginsenoside heterogeneity in cell cutlures of Panax notoginseng by addition of jasmonates. J Biosci Bioeng 93:48-53 https://doi.org/10.1016/S1389-1723(02)80053-6
  66. Woo SS, Song JS, Lee JY, In DS, Chung HJ, Liu JR, Choi DW (2004) Selection of high ginsenoside producing ginseng hairy root lines using targeted metabolic analysis. Phytochem 65:2751-2761 https://doi.org/10.1016/j.phytochem.2004.08.039
  67. Yoshikawa T, Furuya T (1987) Saponin production by cultures of Panax ginseng transformed with Agrobacterium rhizogenes. Plant Cell Rep 6:449-453 https://doi.org/10.1007/BF00272780
  68. Yang DC, Choi YE (2000) Production of transgenic plants via Agrobacterium rhizogenes-mediated transformation of Panax ginseng. Plant Cell Rep 10:491-496 https://doi.org/10.1007/s002990050761
  69. Yu KW, Gao W, Hahn E J, Paek KY (2002) Jasmonic acid improves ginsenoside accumulation in adventitious root culture of Panax ginseng C.A. Meyer. Biochem Eng J 11:211-215 https://doi.org/10.1016/S1369-703X(02)00029-3
  70. Yun TK (2001) Panax ginseng - an non-organ-specific cancer preventive? Lancet Oncol 2:49-55 https://doi.org/10.1016/S1470-2045(00)00196-0
  71. Yu KW, Gao W, Son SH, Paek KY (2000) Improvement of ginsenoside productivity by jasmonic acid and some other elictors in hairy root culture of ginseng (Panax ginseng C.A. Meyer). In Vitro Cell Dev Biol-Plant 36:424-428 https://doi.org/10.1007/s11627-000-0077-4
  72. Yue CJ, Zhong JJ (2005) Purification and characterization fo UDPG:ginsenoside Rd glucosyltransferase from suspended cells of Panax notoginseng. Process Biochem 40:3742-3748 https://doi.org/10.1016/j.procbio.2005.05.001
  73. Yue CJ, Zhou X, Zhong JJ (2008) Protopanaxadiol 6-hydroxylase and its role in regulating the ginsenoside heterogeneity in Panax notoginseng cells. Biotechnol Bioeng 100:933-940 https://doi.org/10.1002/bit.21829
  74. Zheng Z, Wu M (2004) Cadmium treatment enhances the production of alkaloid secondary metabolites in Catharanthus roseus. Plant Science(Limerick) 166:507-514 https://doi.org/10.1016/j.plantsci.2003.10.022