전체메뉴
검색
Article Search

JMB Journal of Microbiolog and Biotechnology

QR Code QR Code

Research article

References

  1. Bae M, Jang S, Lim JW, Kang J, Bak EJ, Cha JH, et al. 2014. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils. J. Ginseng Res. 38: 8-15.
    Pubmed PMC CrossRef
  2. Lee CH, Kim JH. 2014. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J. Ginseng Res. 38: 161-166.
    Pubmed PMC CrossRef
  3. Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH. 2012. Ginseng in traditional herbal prescriptions. J. Ginseng Res. 36: 225-241.
    Pubmed PMC CrossRef
  4. Christensen LP. 2008. Ginsenosides. Chemistry, biosynthesis, analysis, and potential health effects. Adv. Food Nutr. Res. 55: 1-99.
    CrossRef
  5. Corbit RM, Ferreira JF, Ebbs SD, Murphy LL. 2005. Simplified extraction of ginsenosides from American ginseng (Panax quinquefolius L.) for high-performance liquid chromatographyultraviolet analysis. J. Agric. Food Chem. 53: 9867-9873.
    Pubmed CrossRef
  6. Nguyen H T, S ong GY, Kim JA, H yun JH, Kang H K, K im YH. 2010. D ammarane-type saponins f rom the f lower buds of Panax ginseng and their effects on human leukemia cells. Bioorg. Med. Chem. Lett. 20: 309-314.
    Pubmed CrossRef
  7. Qu C, Bai Y, Jin X, Wang Y, Zhang K, You J, et al. 2009. Study on ginsenosides in different parts and ages of Panax quinquefolius L. Food Chem. 115: 340-346.
    CrossRef
  8. Shi W, Wang Y, Li J, Zhang H, Ding L. 2007. Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chem. 102: 664-668.
    CrossRef
  9. Hasegawa H. 2004. Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J. Pharmacol. Sci. 95: 153-157.
    Pubmed CrossRef
  10. Akao T, Kanaoka M, Kobashi K. 1998. Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration measurement of compound K by enzyme immunoassay. Biol. Pharm. Bull. 21: 245-249.
    Pubmed CrossRef
  11. Liu Y, Zhang JW, Li W, Ma H, Sun J, Deng MC, Yang L. 2006. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol. Sci. 91: 356-364.
    Pubmed CrossRef
  12. Baek NI, Kim DS, Lee YH, Park JD, Lee CB, Kim SI. 1995. Cytotoxicities of ginseng saponins and their degradation products against some cancer cell lines. Arch. Pharm. Res. 18: 164-168.
    CrossRef
  13. Popovich DG, Kitts DD. 2004. Generation of ginsenosides Rg3 and Rh2 from North American ginseng. Phytochemistry 65:337-344.
    CrossRef
  14. Park CS, Yoo MH, Noh KH, Oh DK. 2010. Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl. Microbiol. Biotechnol. 87: 9-19.
    Pubmed CrossRef
  15. Siddiqi MZ, Siddiqi MH, Kim YJ, J in Y, Huq MA, Yang DC. 2015. Effect of fermented red ginseng extract enriched in ginsenoside Rg3 on the differentiation and mineralization of preosteoblastic MC3T3-E1 cells. J. Med. Food 18: 1-7.
    Pubmed PMC CrossRef
  16. Wang Y, Choi KD, Yu H, Jin F, Im WT. 2016. Production of ginsenoside F1 using commercial enzyme Cellulase KN. J. Ginseng Res. 40: 121-126.
    Pubmed PMC CrossRef
  17. An DS, Cui CH, Lee HG, Wang L, Kim SC, Lee ST, et al. 2010. Identification and characterization of a novel Terrabacter ginsenosidimutans sp. nov. beta-glucosidase that transforms ginsenoside Rb1 into the rare gypenosides XVII and LXXV. Appl. Environ. Microbiol. 76: 5827-5836.
    Pubmed PMC CrossRef
  18. Yoo DS, Rho HS, Lee YG, Yeom MH, Kim DH, Lee SL, et al. 2011. Ginsenoside F1 modulates cellular responses of skin Melanoma Cells. J. Ginseng Res. 35: 86-91.
    CrossRef
  19. Lee EH, Cho SY, Kim SJ, Shin ES, Chang HK, Kim DH, et al. 2003. Ginsenoside F1 protects human HaCaT keratinocytes from ultraviolet-B-induced apoptosis by maintaining constant levels of Bcl-2. J. Invest. Dermatol. 121: 607-613.
    Pubmed CrossRef
  20. Ko SR, Choi KJ, Suzuki K, Suzuki Y. 2003. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1. Chem. Pharm. Bull. 51: 404-408.
    CrossRef
  21. Kim YS, Yoo MH, Lee GW, Choi JG, Kim KR, Oh DK. 2011. Ginsenoside F1 production from ginsenoside Rg1 by a purified β-glucosidase from Fusarium moniliforme var. subglutinans. Biotechnol. Lett. 33: 2457-2461.
    Pubmed CrossRef
  22. Wang D, Yu H, Song J, Xu Y, Jin F. 2012. Enzyme kinetics of ginsenosidase type IV hydrolyzing 6-O-multi-glycosides of protopanaxatriol type ginsenosides. Process Biochem. 47:133-138.
    CrossRef
  23. Wei Y, Zhao W, Zhang Q, Zhao Y, Zhang Y. 2011. Purification and characterization of a novel and unique ginsenoside Rg 1-hydrolyzing β-D-glucosidase from Penicillium sclerotiorum. Acta Biochim. Biophys. Sin. 43: 226-231.
    Pubmed CrossRef
  24. An DS, Cui CH, Sung BH, Yang HC, Kim SC, Lee ST, et al. 2012. Characterization of a novel ginsenoside-hydrolyzing α-L-arabinofuranosidase, AbfA, from Rhodanobacter ginsenosidimutans Gsoil 3054T. Appl. Microbiol. Biotechnol. 94: 673-682.
    Pubmed CrossRef

Article

Research article

J. Microbiol. Biotechnol. 2017; 27(9): 1559-1565

Published online September 28, 2017 https://doi.org/10.4014/jmb.1703.03006

Copyright © The Korean Society for Microbiology and Biotechnology.

Gram-Scale Production of Ginsenoside F1 Using a Recombinant Bacterial β-Glucosidase

Dong-Shan An 1, Chang-Hao Cui 2, Muhammad Zubair Siddiqi 3, 4, Hong Shan Yu 5, Feng-Xie Jin 5, Song-Gun Kim 1, 6 and Wan-Taek Im 3, 4*

1Biological Resource Center/Korean Collection for Type Cultures (KCTC), Korea Research Institute of Bioscience and Biotechnology, Jeongeup 56212, Republic of Korea, 2KAIST Institute for Biocentury, Korea Advanced Institute of Science and Technology, Daejeon 34141, Republic of Korea, 3Department of Biotechnology, Hankyong National University, Anseong 17579, Republic of Korea, 4Center for Genetic Information, Graduate School of Bio and Information Technology, Hankyong National University, Anseong 17579, Republic of Korea, 5College of Biotechnology, Dalian Polytechnic University, Dalian 116034, P.R. China, 5University of Science and Technology (UST), Daejeon 34113, Republic of Korea

Received: March 6, 2017; Accepted: June 19, 2017

Abstract

Naturally occurring ginsenoside F1 (20-O-β-D-glucopyranosyl-20(S)-protopanaxatriol) is rare.
Here, we produced gram-scale quantities of ginsenoside F1 from a crude protopanaxatriol
saponin mixture comprised mainly of Re and Rg1 through enzyme-mediated biotransformation
using recombinant β-glucosidase (BgpA) cloned from a soil bacterium, Terrabacter
ginsenosidimutans Gsoil 3082T. In a systematic step-by-step process, the concentrations of
substrate, enzyme, and NaCl were determined for maximal production of F1. At an optimized
NaCl concentration of 200 mM, the protopanaxatriol saponin mixture (25 mg/ml) was incubated
with recombinant BgpA (20 mg/ml) for 3 days in a 2.4 L reaction. Following octadecylsilyl
silica gel column chromatography, 9.6 g of F1 was obtained from 60 g of substrate mixture at
95% purity, as assessed by chromatography. These results represent the first report of gramscale
F1 production via recombinant enzyme-mediated biotransformation.

Keywords: Protopanaxatriol, bioconversion, gram-scale, glycoside hydrolase family 3, rare ginsenoside

References

  1. Bae M, Jang S, Lim JW, Kang J, Bak EJ, Cha JH, et al. 2014. Protective effect of Korean Red Ginseng extract against Helicobacter pylori-induced gastric inflammation in Mongolian gerbils. J. Ginseng Res. 38: 8-15.
    Pubmed KoreaMed CrossRef
  2. Lee CH, Kim JH. 2014. A review on the medicinal potentials of ginseng and ginsenosides on cardiovascular diseases. J. Ginseng Res. 38: 161-166.
    Pubmed KoreaMed CrossRef
  3. Park HJ, Kim DH, Park SJ, Kim JM, Ryu JH. 2012. Ginseng in traditional herbal prescriptions. J. Ginseng Res. 36: 225-241.
    Pubmed KoreaMed CrossRef
  4. Christensen LP. 2008. Ginsenosides. Chemistry, biosynthesis, analysis, and potential health effects. Adv. Food Nutr. Res. 55: 1-99.
    CrossRef
  5. Corbit RM, Ferreira JF, Ebbs SD, Murphy LL. 2005. Simplified extraction of ginsenosides from American ginseng (Panax quinquefolius L.) for high-performance liquid chromatographyultraviolet analysis. J. Agric. Food Chem. 53: 9867-9873.
    Pubmed CrossRef
  6. Nguyen H T, S ong GY, Kim JA, H yun JH, Kang H K, K im YH. 2010. D ammarane-type saponins f rom the f lower buds of Panax ginseng and their effects on human leukemia cells. Bioorg. Med. Chem. Lett. 20: 309-314.
    Pubmed CrossRef
  7. Qu C, Bai Y, Jin X, Wang Y, Zhang K, You J, et al. 2009. Study on ginsenosides in different parts and ages of Panax quinquefolius L. Food Chem. 115: 340-346.
    CrossRef
  8. Shi W, Wang Y, Li J, Zhang H, Ding L. 2007. Investigation of ginsenosides in different parts and ages of Panax ginseng. Food Chem. 102: 664-668.
    CrossRef
  9. Hasegawa H. 2004. Proof of the mysterious efficacy of ginseng: basic and clinical trials: metabolic activation of ginsenoside: deglycosylation by intestinal bacteria and esterification with fatty acid. J. Pharmacol. Sci. 95: 153-157.
    Pubmed CrossRef
  10. Akao T, Kanaoka M, Kobashi K. 1998. Appearance of compound K, a major metabolite of ginsenoside Rb1 by intestinal bacteria, in rat plasma after oral administration measurement of compound K by enzyme immunoassay. Biol. Pharm. Bull. 21: 245-249.
    Pubmed CrossRef
  11. Liu Y, Zhang JW, Li W, Ma H, Sun J, Deng MC, Yang L. 2006. Ginsenoside metabolites, rather than naturally occurring ginsenosides, lead to inhibition of human cytochrome P450 enzymes. Toxicol. Sci. 91: 356-364.
    Pubmed CrossRef
  12. Baek NI, Kim DS, Lee YH, Park JD, Lee CB, Kim SI. 1995. Cytotoxicities of ginseng saponins and their degradation products against some cancer cell lines. Arch. Pharm. Res. 18: 164-168.
    CrossRef
  13. Popovich DG, Kitts DD. 2004. Generation of ginsenosides Rg3 and Rh2 from North American ginseng. Phytochemistry 65:337-344.
    CrossRef
  14. Park CS, Yoo MH, Noh KH, Oh DK. 2010. Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl. Microbiol. Biotechnol. 87: 9-19.
    Pubmed CrossRef
  15. Siddiqi MZ, Siddiqi MH, Kim YJ, J in Y, Huq MA, Yang DC. 2015. Effect of fermented red ginseng extract enriched in ginsenoside Rg3 on the differentiation and mineralization of preosteoblastic MC3T3-E1 cells. J. Med. Food 18: 1-7.
    Pubmed KoreaMed CrossRef
  16. Wang Y, Choi KD, Yu H, Jin F, Im WT. 2016. Production of ginsenoside F1 using commercial enzyme Cellulase KN. J. Ginseng Res. 40: 121-126.
    Pubmed KoreaMed CrossRef
  17. An DS, Cui CH, Lee HG, Wang L, Kim SC, Lee ST, et al. 2010. Identification and characterization of a novel Terrabacter ginsenosidimutans sp. nov. beta-glucosidase that transforms ginsenoside Rb1 into the rare gypenosides XVII and LXXV. Appl. Environ. Microbiol. 76: 5827-5836.
    Pubmed KoreaMed CrossRef
  18. Yoo DS, Rho HS, Lee YG, Yeom MH, Kim DH, Lee SL, et al. 2011. Ginsenoside F1 modulates cellular responses of skin Melanoma Cells. J. Ginseng Res. 35: 86-91.
    CrossRef
  19. Lee EH, Cho SY, Kim SJ, Shin ES, Chang HK, Kim DH, et al. 2003. Ginsenoside F1 protects human HaCaT keratinocytes from ultraviolet-B-induced apoptosis by maintaining constant levels of Bcl-2. J. Invest. Dermatol. 121: 607-613.
    Pubmed CrossRef
  20. Ko SR, Choi KJ, Suzuki K, Suzuki Y. 2003. Enzymatic preparation of ginsenosides Rg2, Rh1, and F1. Chem. Pharm. Bull. 51: 404-408.
    CrossRef
  21. Kim YS, Yoo MH, Lee GW, Choi JG, Kim KR, Oh DK. 2011. Ginsenoside F1 production from ginsenoside Rg1 by a purified β-glucosidase from Fusarium moniliforme var. subglutinans. Biotechnol. Lett. 33: 2457-2461.
    Pubmed CrossRef
  22. Wang D, Yu H, Song J, Xu Y, Jin F. 2012. Enzyme kinetics of ginsenosidase type IV hydrolyzing 6-O-multi-glycosides of protopanaxatriol type ginsenosides. Process Biochem. 47:133-138.
    CrossRef
  23. Wei Y, Zhao W, Zhang Q, Zhao Y, Zhang Y. 2011. Purification and characterization of a novel and unique ginsenoside Rg 1-hydrolyzing β-D-glucosidase from Penicillium sclerotiorum. Acta Biochim. Biophys. Sin. 43: 226-231.
    Pubmed CrossRef
  24. An DS, Cui CH, Sung BH, Yang HC, Kim SC, Lee ST, et al. 2012. Characterization of a novel ginsenoside-hydrolyzing α-L-arabinofuranosidase, AbfA, from Rhodanobacter ginsenosidimutans Gsoil 3054T. Appl. Microbiol. Biotechnol. 94: 673-682.
    Pubmed CrossRef