Applied Microbiology and Biotechnology

, Volume 87, Issue 1, pp 9–19

Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases

  • Chang-Su Park
  • Mi-Hyun Yoo
  • Kyeong-Hwan Noh
  • Deok-Kun Oh
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Abstract

Ginsenosides are the principal components responsible for the pharmaceutical activities of ginseng. The minor ginsenosides, which are also pharmaceutically active, can be produced via the hydrolysis of the sugar moieties in the major ginsenosides using acid hydrolytic, heating, microbial, and enzymatic transformation techniques. The enzymatic method has a profound potential for ginsenoside transformation, owing to its high specificity, yield, and productivity, and this method is increasingly being recognized as a useful tool in structural modification and metabolism studies. In this article, the transformation methods of ginsenosides, the characterization of microbial glycosidases with ginsenoside hydrolyzing activities, and the enzymatic production of minor ginsenosides are reviewed. Moreover, the conversions of ginsenosides using cell extracts from food microorganisms and recombinant thermostable β-d-glycosidases are proposed as feasible methods for use in industrial processes.

Keywords

Ginsenosides Ginsenoside hydrolyzing enzyme Ginsenoside biotransformation Glycosidase Enzyme characterization 

References

  1. Akiba T, Nishio M, Matsui I, Harata K (2004) X-ray structure of a membrane-bound beta-glycosidase from the hyperthermophilic archaeon Pyrococcus horikoshii. Proteins 57:422–431CrossRefGoogle Scholar
  2. Andreea Neculai M, Ivanov D, Bernards MA (2009) Partial purification and characterization of three ginsenoside-metabolizing beta-glucosidases from Pythium irregulare. Phytochemistry 70:1948–1957CrossRefGoogle Scholar
  3. Bae EA, Choo MK, Park EK, Park SY, Shin HY, Kim DH (2002) Metabolism of ginsenoside Rc by human intestinal bacteria and its related antiallergic activity. Biol Pharm Bull 25:743–747CrossRefGoogle Scholar
  4. Bae EA, Shin JE, Kim DH (2005) Metabolism of ginsenoside Re by human intestinal microflora and its estrogenic effect. Biol Pharm Bull 28:1903–1908CrossRefGoogle Scholar
  5. Burdock GA, Carabin IG (2004) Generally recognized as safe (GRAS): history and description. Toxicol Lett 150:3–18CrossRefGoogle Scholar
  6. Chae S, Kang KA, Chang WY, Kim MJ, Lee SJ, Lee YS, Kim HS, Kim DH, Hyun JW (2009) Effect of compound K, a metabolite of ginseng saponin, combined with gamma-ray radiation in human lung cancer cells in vitro and in vivo. J Agric Food Chem 57:5777–5782CrossRefGoogle Scholar
  7. Chang KH, Jee HS, Lee NK, Park SH, Lee NW, Paik HD (2009) Optimization of the enzymatic production of 20(S)-ginsenoside Rg3 from white ginseng extract using response surface methodology. N Biotechnol 26:181–186CrossRefGoogle Scholar
  8. Chen G, Yang M, Lu Z, Zhang J, Huang H, Liang Y, Guan S, Song Y, Wu L, Guo DA (2007) Microbial transformation of 20(S)-protopanaxatriol-type saponins by Absidia coerulea. J Nat Prod 70:1203–1206CrossRefGoogle Scholar
  9. Chen GT, Yang M, Song Y, Lu ZQ, Zhang JQ, Huang HL, Wu LJ, Guo DA (2008) Microbial transformation of ginsenoside Rb1 by Acremonium strictum. Appl Microbiol Biotechnol 77:1345–1350CrossRefGoogle Scholar
  10. Cheng LQ, Kim MK, Lee JW, Lee YJ, Yang DC (2006) Conversion of major ginsenoside Rb1 to ginsenoside F2 by Caulobacter leidyia. Biotechnol Lett 28:1121–1127CrossRefGoogle Scholar
  11. Cheng LQ, Na JR, Kim MK, Bang MH, Yang DC (2007) Microbial conversion of ginsenoside Rb1 to minor ginsenoside F2 and gypenoside XVII by Intrasporangium sp. GS603 isolated from soil. J Microbiol Biotechnol 17:1937–1943Google Scholar
  12. Cheng LQ, Na JR, Bang MH, Kim MK, Yang DC (2008) Conversion of major ginsenoside Rb1 to 20(S)-ginsenoside Rg3 by Microbacterium sp. GS514. Phytochemistry 69:218–224CrossRefGoogle Scholar
  13. Chi H, Ji GE (2005) Transformation of ginsenosides Rb1 and Re from Panax ginseng by food microorganisms. Biotechnol Lett 27:765–771CrossRefGoogle Scholar
  14. Chi H, Kim DH, Ji GE (2005) Transformation of ginsenosides Rb2 and Rc from Panax ginseng by food microorganisms. Biol Pharm Bull 28:2102–2105CrossRefGoogle Scholar
  15. Chi H, Lee BH, You HJ, Park MS, Ji GE (2006) Differential transformation of ginsenosides from Panax ginseng by lactic acid bacteria. J Microbiol Biotechnol 16:1629–1633Google Scholar
  16. Czjzek M, Ben David A, Bravman T, Shoham G, Henrissat B, Shoham Y (2005) Enzyme-substrate complex structures of a GH39 beta-xylosidase from Geobacillus stearothermophilus. J Mol Biol 353:838–846CrossRefGoogle Scholar
  17. Dong A, Ye M, Guo H, Zheng J, Guo D (2003) Microbial transformation of ginsenoside Rb1 by Rhizopus stolonifer and Curvularia lunata. Biotechnol Lett 25:339–344CrossRefGoogle Scholar
  18. Fontes EAF, Passos FML, Passos FJV (2001) A mechanistical mathematical model to predict lactose hydrolysis by beta-galactosidase in a permeabilized cell mass of Kluyveromyces lactis: validity and sensitivity analysis. Process Biochem 37:267–274CrossRefGoogle Scholar
  19. Gloster TM, Roberts S, Perugino G, Rossi M, Moracci M, Panday N, Terinek M, Vasella A, Davies GJ (2006) Structural, kinetic, and thermodynamic analysis of glucoimidazole-derived glycosidase inhibitors. Biochemistry 45:11879–11884CrossRefGoogle Scholar
  20. Haki GD, Rakshit SK (2003) Developments in industrially important thermostable enzymes: a review. Biores Technol 89:17–34CrossRefGoogle Scholar
  21. Hakulinen N, Paavilainen S, Korpela T, Rouvinen J (2000) The crystal structure of beta-glucosidase from Bacillus circulans sp. alkalophilus: ability to form long polymeric assemblies. J Struct Biol 129:69–79CrossRefGoogle Scholar
  22. Han BH, Park MH, Han YN, Woo LK, Sankawa U, Yahara S, Tanaka O (1982) Degradation of ginseng saponins under mild acidic conditions. Planta Med 44:146–149CrossRefGoogle Scholar
  23. Han Y, Sun B, Hu X, Zhang H, Jiang B, Spranger MI, Zhao Y (2007) Transformation of bioactive compounds by Fusarium sacchari fungus isolated from the soil-cultivated ginseng. J Agric Food Chem 55:9373–9379CrossRefGoogle Scholar
  24. Hasegawa H, Sung JH, Matsumiya S, Uchiyama M (1996) Main ginseng saponin metabolites formed by intestinal bacteria. Planta Med 62:453–457CrossRefGoogle Scholar
  25. Henrissat B (1991) A classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 280:309–316Google Scholar
  26. Hovel K, Shallom D, Niefind K, Belakhov V, Shoham G, Baasov T, Shoham Y, Schomburg D (2003) Crystal structure and snapshots along the reaction pathway of a family 51 alpha-l-arabinofuranosidase. EMBO J 22:4922–4932CrossRefGoogle Scholar
  27. Hyun C, Lee BH, You HJ, Park MS, Ji GE (2006) Differential transformation of ginsenosides form Panax ginseng by lactic acid bacteria. J Microbiol Biotechnol 16:1629–1633Google Scholar
  28. Isorna P, Polaina J, Latorre-Garcia L, Canada FJ, Gonzalez B, Sanz-Aparicio J (2007) Crystal structures of Paenibacillus polymyxa beta-glucosidase B complexes reveal the molecular basis of substrate specificity and give new insights into the catalytic machinery of family I glycosidases. J Mol Biol 371:1204–1218CrossRefGoogle Scholar
  29. Kang KS, Kim HY, Baek SH, Yoo HH, Park JH, Yokozawa T (2007) Study on the hydroxyl radical scavenging activity changes of ginseng and ginsenoside-Rb2 by heat processing. Biol Pharm Bull 30:724–728CrossRefGoogle Scholar
  30. Karikura M, Miyase T, Tanizawa H, Taniyama T, Takino Y (1991) Studies on absorption, distribution, excretion and metabolism of ginseng saponins. VII. Comparison of the decomposition modes of ginsenoside-Rb1 and -Rb2 in the digestive tract of rats. Chem Pharm Bull (Tokyo) 39:2357–2356Google Scholar
  31. Kim MK, Lee JW, Lee KY, Yang DC (2005) Microbial conversion of major ginsenoside Rb1 to pharmaceutically active minor ginsenoside Rd. J Microbiol 43:456–462Google Scholar
  32. Kim BH, Lee SY, Cho HJ, You SN, Kim YJ, Park YM, Lee JK, Baik MY, Park CS, Ahn SC (2006) Biotransformation of Korean Panax ginseng by pectinex. Biol Pharm Bull 29:2472–2478CrossRefGoogle Scholar
  33. Kim SJ, Lee CM, Kim MY, Yeo YS, Yoon SH, Kang HC, Koo BS (2007) Screening and characterization of an enzyme with beta-glucosidase activity from environmental DNA. J Microbiol Biotechnol 17:905–912Google Scholar
  34. Ko SR, Choi KJ, Suzuki K, Suzuki Y (2003) Enzymatic preparation of ginsenosides Rg2, Rh1, and F1. Chem Pharm Bull (Tokyo) 51:404–408CrossRefGoogle Scholar
  35. Ko SR, Suzuki Y, Suzuki K, Choi KJ, Cho BG (2007) Marked production of ginsenosides Rd, F2, Rg3, and compound K by enzymatic method. Chem Pharm Bull (Tokyo) 55:1522–1527CrossRefGoogle Scholar
  36. Kondo A, Liu Y, Furuta M, Fujita Y, Matsumoto T, Fukuda H (2000) Preparation of high activity whole cell biocatalyst by permeabilization of recombinant flocculent yeast with alcohol. Enzyme Microb Technol 27:806–811CrossRefGoogle Scholar
  37. Lee SY, Choi JH, Xu Z (2003) Microbial cell-surface display. Trends Biotechnol 21:45–52CrossRefGoogle Scholar
  38. Lee HU, Bae EA, Han MJ, Kim NJ, Kim DH (2005) Hepatoprotective effect of ginsenoside Rb1 and compound K on tert-butyl hydroperoxide-induced liver injury. Liver Int 25:1069–1073CrossRefGoogle Scholar
  39. Lee YJ, Kim HY, Kang KS, Lee JG, Yokozawa T, Park JH (2008) The chemical and hydroxyl radical scavenging activity changes of ginsenoside-Rb1 by heat processing. Bioorg Med Chem Lett 18:4515–4520CrossRefGoogle Scholar
  40. Lee SM, Shon HJ, Choi CS, Hung TM, Min BS, Bae K (2009) Ginsenosides from heat processed ginseng. Chem Pharm Bull (Tokyo) 57:92–94CrossRefGoogle Scholar
  41. Liang Y, Zhao S (2008) Progress in understanding of ginsenoside biosynthesis. Plant Biol (Stuttg) 10:415–421CrossRefGoogle Scholar
  42. Liu ZQ, Luo XY, Liu GZ, Chen YP, Wang ZC, Sun YX (2003) In vitro study of the relationship between the structure of ginsenoside and its antioxidative or prooxidative activity in free radical induced hemolysis of human erythrocytes. J Agric Food Chem 51:2555–2558CrossRefGoogle Scholar
  43. Miyanaga A, Koseki T, Miwa Y, Mese Y, Nakamura S, Kuno A, Hirabayashi J, Matsuzawa H, Wakagi T, Shoun H, Fushinobu S (2006) The family 42 carbohydrate-binding module of family 54 alpha-l-arabinofuranosidase specifically binds the arabinofuranose side chain of hemicellulose. Biochem J 399:503–511CrossRefGoogle Scholar
  44. Mochizuki M, Yoo YC, Matsuzawa K, Sato K, Saiki I, Tono-oka S, Samukawa K, Azuma I (1995) Inhibitory effect of tumor metastasis in mice by saponins, ginsenoside-Rb2, 20(R)- and 20(S)-ginsenoside-Rg3, of red ginseng. Biol Pharm Bull 18:1197–1202Google Scholar
  45. Ni HX, Yu NJ, Yang XH (2009) The study of ginsenoside on PPARgamma expression of mononuclear macrophage in type 2 diabetes. Mol Biol Rep. doi:10.1007/s11033-009-9864-0 Google Scholar
  46. Nijikken Y, Tsukada T, Igarashi K, Samejima M, Wakagi T, Shoun H, Fushinobu S (2007) Crystal structure of intracellular family 1 beta-glucosidase BGL1A from the basidiomycete Phanerochaete chrysosporium. FEBS Lett 581:1514–1520CrossRefGoogle Scholar
  47. Noh KH, Oh DK (2009) Production of the rare ginsenosides compound K, compound Y, and compound Mc by a thermostable beta-glycosidase from Sulfolobus acidocaldarius. Biol Pharm Bull 32:1830–1835CrossRefGoogle Scholar
  48. Noh KH, Son JW, Kim HJ, Oh DK (2009) Ginsenoside compound K production from ginseng root extract by a thermostable beta-glycosidase from Sulfolobus solfataricus. Biosci Biotechnol Biochem 73:316–321CrossRefGoogle Scholar
  49. Paes G, Skov LK, O'Donohue MJ, Remond C, Kastrup JS, Gajhede M, Mirza O (2008) The structure of the complex between a branched pentasaccharide and Thermobacillus xylanilyticus GH-51 arabinofuranosidase reveals xylan-binding determinants and induced fit. Biochemistry 47:7441–7451CrossRefGoogle Scholar
  50. Park SY, Bae EA, Sung JH, Lee SK, Kim DH (2001) Purification and characterization of ginsenoside Rb1-metabolizing beta-glucosidase from Fusobacterium K-60, a human intestinal anaerobic bacterium. Biosci Biotechnol Biochem 65:1163–1169CrossRefGoogle Scholar
  51. Pozzo T, Pasten JL, Karlsson EN, Logan DT (2010) Structural and functional analyses of beta-glucosidase 3B from Thermotoga neapolitana: A thermostable three-domain representative of glycoside hydrolase 3. J Mol Biol 397:724–739CrossRefGoogle Scholar
  52. Ruan CC, Zhang H, Zhang LX, Liu Z, Sun GZ, Lei J, Qin YX, Zheng YN, Li X, Pan HY (2009) Biotransformation of ginsenoside Rf to Rh1 by recombinant beta-glucosidase. Molecules 14:2043–2048CrossRefGoogle Scholar
  53. Shin HY, Lee JH, Lee JY, Han YO, Han MJ, Kim DH (2003a) Purification and characterization of ginsenoside Ra-hydrolyzing beta-d-xylosidase from Bifidobacterium breve K-110, a human intestinal anaerobic bacterium. Biol Pharm Bull 26:1170–1173CrossRefGoogle Scholar
  54. Shin HY, Park SY, Sung JH, Kim DH (2003b) Purification and characterization of alpha-L-arabinopyranosidase and alpha-l-arabinofuranosidase from Bifidobacterium breve K-110, a human intestinal anaerobic bacterium metabolizing ginsenoside Rb2 and Rc. Appl Environ Microbiol 69:7116–7123CrossRefGoogle Scholar
  55. Son JW, Kim HJ, Oh DK (2008) Ginsenoside Rd production from the major ginsenoside Rb1 by beta-glucosidase from Thermus caldophilus. Biotechnol Lett 30:713–716CrossRefGoogle Scholar
  56. Song X, Zang L, Hu S (2009) Amplified immune response by ginsenoside-based nanoparticles (ginsomes). Vaccine 27:2306–2311CrossRefGoogle Scholar
  57. Stavro PM, Woo M, Heim TF, Leiter LA, Vuksan V (2005) North American ginseng exerts a neutral effect on blood pressure in individuals with hypertension. Hypertension 46:406–411CrossRefGoogle Scholar
  58. Su J-H, Xu J-H, Lu W-Y, Lin G-Q (2006) Enzymatic transformation of ginsenoside Rg3 to Rh2 using newly isolated Fusarium proliferatum ECU 2042. J Mol Catal B Enzym 38:113–118CrossRefGoogle Scholar
  59. Tansakul P, Shibuya M, Kushiro T, Ebizuka Y (2006) Dammarenediol-II synthase, the first dedicated enzyme for ginsenoside biosynthesis, in Panax ginseng. FEBS Lett 580:5143–5149CrossRefGoogle Scholar
  60. Tawab MA, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M (2003) Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos 31:1065–1071CrossRefGoogle Scholar
  61. Taylor EJ, Smith NL, Turkenburg JP, D'Souza S, Gilbert HJ, Davies GJ (2006) Structural insight into the ligand specificity of a thermostable family 51 arabinofuranosidase, Araf51, from Clostridium thermocellum. Biochem J 395:31–37CrossRefGoogle Scholar
  62. Vandermarliere E, Bourgois TM, Winn MD, van Campenhout S, Volckaert G, Delcour JA, Strelkov SV, Rabijns A, Courtin CM (2009) Structural analysis of a glycoside hydrolase family 43 arabinoxylan arabinofuranohydrolase in complex with xylotetraose reveals a different binding mechanism compared with other members of the same family. Biochem J 418:39–47CrossRefGoogle Scholar
  63. Vincent F, Gloster TM, Macdonald J, Morland C, Stick RV, Dias FM, Prates JA, Fontes CM, Gilbert HJ, Davies GJ (2004) Common inhibition of both beta-glucosidases and beta-mannosidases by isofagomine lactam reflects different conformational itineraries for pyranoside hydrolysis. Chembiochem 5:1596–1599CrossRefGoogle Scholar
  64. Wang CZ, Aung HH, Ni M, Wu JA, Tong R, Wicks S, He TC, Yuan CS (2007) Red American ginseng: ginsenoside constituents and antiproliferative activities of heat-processed Panax quinquefolius roots. Planta Med 73:669–674CrossRefGoogle Scholar
  65. Yan Q, Zhou W, Li X, Feng M, Zhou P (2008a) Purification method improvement and characterization of a novel ginsenoside-hydrolyzing beta-glucosidase from Paecilomyces bainier sp. 229. Biosci Biotechnol Biochem 72:352–359CrossRefGoogle Scholar
  66. Yan Q, Zhou XW, Zhou W, Li XW, Feng MQ, Zhou P (2008b) Purification and properties of a novel beta-glucosidase, hydrolyzing ginsenoside Rb1 to compound K, from Paecilomyces bainier. J Microbiol Biotechnol 18:1081–1089Google Scholar
  67. Yang DC, Yang KJ, Choi YE (2001) Production of red ginseng specific ginsenosides (Rg2, Rg3, Rh1 and Rh2) from Agrobacterium—transformed hairy roots of Panax ginseng by heat treatment. J Photosci 8:19–22Google Scholar
  68. Yang JK, Yoon HJ, Ahn HJ, Lee BI, Pedelacq JD, Liong EC, Berendzen J, Laivenieks M, Vieille C, Zeikus GJ, Vocadlo DJ, Withers SG, Suh SW (2004) Crystal structure of beta-d-xylosidase from Thermoanaerobacterium saccharolyticum, a family 39 glycoside hydrolase. J Mol Biol 335:155–165CrossRefGoogle Scholar
  69. Yu H, Ma X, Guo Y, Jin F (1999) Purification and characterization of ginsenoside-beta-glucosidase. J Ginseng Res 23:50–54Google Scholar
  70. Yu H, Gong J, Zhang C, Jin F (2002) Purification and characterization of ginsenoside-alpha-l-rhamnosidase. Chem Pharm Bull (Tokyo) 50:175–178CrossRefGoogle Scholar
  71. Yu H, Liu H, Zhang C, Tan D, Lu M, Jin F (2004) Purification and characterization of gypenoside-alpha-l-rhamnosidase hydrolyzing gypenoside-5 into ginsenoside Rd. Process Biochem 39:861–867CrossRefGoogle Scholar
  72. Yu H, Zhang C, Lu M, Sun F, Fu Y, Jin F (2007) Purification and characterization of new special ginsenosidase hydrolyzing multi-glycisides of protopanaxadiol ginsenosides, ginsenosidase type I. Chem Pharm Bull (Tokyo) 55:231–235CrossRefGoogle Scholar
  73. Yue CJ, Zhong JJ (2005) Purification and characterization of UDPG:ginsenoside Rd glucosyltransferase from suspended cells of Panax notoginseng. Process Biochem 40:3742–3748CrossRefGoogle Scholar
  74. Yue CJ, Zhou X, Zhong JJ (2008) Protopanaxadiol 6-hydroxylase and its role in regulating the ginsenoside heterogeneity in Panax notoginseng cells. Biotechnol Bioeng 100:933–940CrossRefGoogle Scholar
  75. Zechel DL, Boraston AB, Gloster T, Boraston CM, Macdonald JM, Tilbrook DM, Stick RV, Davies GJ (2003) Iminosugar glycosidase inhibitors: structural and thermodynamic dissection of the binding of isofagomine and 1-deoxynojirimycin to beta-glucosidases. J Am Chem Soc 125:14313–14323CrossRefGoogle Scholar
  76. Zhao X, Gao L, Wang J, Bi H, Gao J, Du X, Zhou Y, Tai G (2009) A novel ginsenoside Rb1-hydrolyzing beta-d-glucosidase from Cladosprium fulvum. Process Biochem 44:612–618CrossRefGoogle Scholar
  77. Zhou W, Yan Q, Li JY, Zhang XC, Zhou P (2008) Biotransformation of Panax notoginseng saponins into ginsenoside compound K production by Paecilomyces bainier sp. 229. J Appl Microbiol 104:699–706CrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Chang-Su Park
    • 1
  • Mi-Hyun Yoo
    • 1
  • Kyeong-Hwan Noh
    • 1
  • Deok-Kun Oh
    • 1
  1. 1.Department of Bioscience and BiotechnologyKonkuk UniversitySeoulRepublic of Korea

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