Skip to main content
SpringerLink
Log in

Biotransformation of Ginsenoside Rb1 to Ginsenoside CK by Strain XD101: a Safe Bioconversion Strategy

  • Original Article
  • Published:
Applied Biochemistry and Biotechnology Aims and scope Submit manuscript

An Author Correction to this article was published on 22 April 2021

This article has been updated

Abstract

Ginsenoside Rb1 is the main predominant component in Panax species. In this study, an eco-friendly and convenient preparation method for ginsenoside CK has been established, and five strains of β-glucosidase-producing microorganisms were screened out from the soil of a Panax notoginseng planting field using Esculin-R2A agar. Aspergillus niger XD101 showed that it has excellent biocatalytic activity for ginsenosides; one of the isolates can convert ginsenoside Rb1 to CK using extracellular enzyme from the mycelium. Mycelia of A. niger were cultivated in wheat bran media at 30 °C for 11 days. By the removal of mycelia from cultured broth, enzyme salt fractionation by ammonium sulfate (70%, v/v) precipitation, and dialysis, sequentially, crude enzyme preparations from fermentation liquid supernatant were obtained. The enzymatic transformed Rb1 as the following pathways: Rb1→Rd→F2→CK. The optimized reaction conditions are at reaction time of 72 h, in the range of pH 4–5, and temperature of 50–60 °C. Active minor ginsenosides can be obtained by a specific bioconversion via A. niger XD101 producing the ginsenoside-hydrolyzing β-glucosidase. In addition, the crude enzyme can be resulted in producing ginsenoside CK via conversion of ginsenoside Rb1 at high conversion yield (94.4%). FDA generally regarded, A.niger as safe microorganism. Therefore, these results indicate that A. niger XD10 may provide an alternative method to prepare ginsenoside CK without food safety issues in the pharmaceutical industry.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig 1
Fig 2
Fig 3
Fig 4
Fig 5
Fig 6
Fig. 7
Fig 8
Fig 9
Fig 10

Similar content being viewed by others

Change history

References

  1. Park, C. S., Yoo, M. H., Noh, K. H., & Oh, D. K. (2010). Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Applied Microbiology and Biotechnology, 87, 9–19.

    Article  CAS  Google Scholar 

  2. Yoo, M. H., Yeom, S. J., Park, C. S., Lee, K. W., & Oh, D. K. (2011). Production of aglycon protopanaxadiol via compound K by a thermostable β-glycosidase from Pyrococcus furiosus. Applied Microbiology and Biotechnology, 89, 1019–1028.

    Article  CAS  Google Scholar 

  3. Luan, H., Qi, L. X., Hu, Y., Hao, D., Cui, Y., & Yang, L. (2006). Purification and characterization of a novel stable ginsenoside Rb1-hydrolyzing β-D-glucosidase China white jade snail. Process Biochemistry, 41(9), 1974–1980.

    Article  CAS  Google Scholar 

  4. Duan, Z. G., Wei, B., Deng, J. J., Mi, Y., Dong, Y. F., Zhu, C. H., Fu, R. Z., Qu, L. L., & Fan, D. D. (2018). The anti-tumor effect of ginsenoside Rh4 in MCF-7 breast cancer cells in vitro and in vivo. Biochemical and Biophysical Research Communications, 499, 482–487.

    Article  CAS  Google Scholar 

  5. Lin, F., Guo, X., & Lu, W. (2015). Efficient biotransformation of ginsenoside Rb1 to Rd by isolated Aspergillus versicolor, excreting β-glucosidase in the spore production phase of solid culture. Anton Leeuw, 108(5), 1117–1127.

    Article  CAS  Google Scholar 

  6. Upadhyaya, J., Kim, M. J., Kim, Y. H., Ko, S. R., Park, H. W., & Kim, M. K. (2016). Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea. Journal of Ginseng Research, 40, 105–112.

    Article  Google Scholar 

  7. Lei, C., Wu, S. Q., Zhao, C. A., & Yin, C. R. (2016). Microbial conversion of major ginsenosides in ginseng total saponins by Platycodon grandiflorumendophytes. Journal of Ginseng Research, 40, 366–374.

    Article  Google Scholar 

  8. Kim, M. J., Upadhyaya, J., Yun, M. S., Ryu, N. S., Song, Y. E., Park, H. W., Kim, Y. H., & Kim, M. K. (2017). Highly regioselective biotransformation of ginsenoside Rb2 into compound Y and compound K by β-glycosidase purified from Armillaria mellea mycelia. Journal of Ginseng Research, 42, 504–511.

    Article  Google Scholar 

  9. Hwang, C. R., Lee, S. H., Jang, G. Y., Hwang, I. G., Kim, H. Y., Woo, K. S., Lee, J., & Jeong, H. S. (2014). Changes in ginsenoside compositions and antioxidant activities of hydroponic-cultured ginseng roots and leaves with heating temperature. Journal of Ginseng Research, 38(3), 180–186.

    Article  Google Scholar 

  10. Sun, C., Gao, W., Zhao, B., & Cheng, L. (2013). Optimization of the selective preparation of 20(R)-ginsenoside Rg3 catalyzed by d, l-tartaric acid using response surface methodology. Fitoterapia., 84, 213–221.

    Article  CAS  Google Scholar 

  11. Quan, L. H., Kim, Y. J., Li, G. H., Choi, K. T., & Yang, D. C. (2013). Microbial transformation of ginsenoside Rb1 to compound K by Lactobacillus paralimentarius. World Journal of Microbiology and Biotechnology, 29, 1001–1007.

    Article  CAS  Google Scholar 

  12. Song, X., Wu, H., Piao, X., Yin, Z., & Yin, C. (2017). Microbial transformation of ginsenosides extracted from Panax ginseng adventitious roots in an airlift bioreactor. Electronic Journal of Biotechnology, 26, 20–26.

    Article  Google Scholar 

  13. Murthy, H. N., Georgiev, M. I., Kim, Y. S., Jeong, C. S., Kim, S. J., Park, S. Y., & Paek, K. Y. (2014). Ginsenosides: prospective for sustainable biotechnological production. Applied Microbiology and Biotechnology, 98(14), 6243–6254.

    Article  CAS  Google Scholar 

  14. Eom, S. J., Kim, K. T., & Paik, H. D. (2018). Microbial bioconversion of ginsenosides in Panax ginseng and their improved bioactivities. Food Review International, 34, 698–712.

    Article  CAS  Google Scholar 

  15. Ku, S. (2016). Finding and producing probiotic glycosylases for the biocatalysis of ginsenosides: a mini review. Molecules, 21, 645.

    Article  Google Scholar 

  16. Chang, K. H., Jo, M. N., Kim, K. T., & Paik, H. D. (2014). Evaluation of glucosidases of Aspergillus niger strain comparing with other glucosidases in transformation of ginsenoside Rb1 to ginsenosides Rg3. Journal of Ginseng Research, 38, 47–51.

    Article  Google Scholar 

  17. Kim, S. H., Min, J. W., Quan, L. H., Lee, S., Yang, D. U., & Yang, D. C. (2012). Enzymatic transformation of ginsenoside Rb1 by Lactobacillus pentosus strain 6105 from kimchi. Journal of Ginseng Research, 36, 291–297.

    Article  CAS  Google Scholar 

  18. Cui, L., Wu, S. Q., Zhao, C. A., & Yin, C. R. (2016). Microbial conversion of major ginsenosides in ginseng total saponins by Platycodon grandiflorum endophytes. Journal of Ginseng Research, 40, 366–374.

    Article  Google Scholar 

  19. Yan, Q., Zhou, W., Shi, X., Zhou, P., Ju, D., & Feng, M. (2010). Biotransformation pathways of ginsenoside Rb1 to compound K by β-glucosidases in fungus Paecilomyces Bainier sp. 229. Process Biochemistry, 45(9), 1550–1556.

    Article  CAS  Google Scholar 

  20. Quan, L. H., Piao, J. Y., Min, J. W., Kim, H. B., Kim, S. R., Yang, D. U., & Yang, D. C. (2011). Biotransformation of ginsenoside Rb1 to prosapogenins, gypenoside XVII, ginsenoside Rd, ginsenoside F2, and compound K by Leuconostoc mesenteroides DC102. Journal of Ginseng Research, 35, 344.

    Article  CAS  Google Scholar 

  21. Zhao, Y., Lee, H. G., Kim, S. K., Yu, H., Jin, F., & Im, W. T. (2016). Mucilaginibacter pocheonensis sp. nov. with ginsenoside converting activity isolated from soil of ginseng cultivating field. International Journal of Systematic and Evolutionary Microbiology, 66, 2862–2868.

    Article  CAS  Google Scholar 

  22. Chi, H., & Ji, G. E. (2005). Transformation of ginsenosides Rb1 and Re from Panax ginseng by food microorganisms. Biotechnology Letters, 27(11), 765–771.

    Article  CAS  Google Scholar 

  23. Cheng, L. Q., Kim, M. K., Lee, J. W., Lee, Y. J., & Yang, D. C. (2006). Conversion of major ginsenoside Rb1 to ginsenoside F2 by Caulobacter leidyia. Biotechnology Letters, 28(14), 1121–1127.

    Article  CAS  Google Scholar 

  24. Ye, L., Zhou, C. Q., Zhou, W., Zhou, P., Chen, D. F., Liu, X. H., Shi, X. L., & Feng, M. Q. (2010). Biotransformation of ginsenoside Rb1 to ginsenoside Rd by highly substrate-tolerant Paecilomyces bainier 229-7. Bioresource Technology, 101, 7872–7876.

    Article  CAS  Google Scholar 

  25. Feng, L., Xu, C., Li, Z., Dai, Y., Han, H., Yu, S., & Liu, S. (2016). Microbial conversion of ginsenoside Rd from Rb1 by the fungus mutant Aspergillus niger strain TH-10a. Preparative Biochemistry, 46, 336–341.

    Article  CAS  Google Scholar 

  26. Molina, G., Contesini, F. J., & De, R. R. (2016). β-Glucosidase from Aspergillus//GUPTA V K, Ed. New and future developments in microbial biotechnology and bioengineering. Amsterdam, 155–169.

  27. Yang, X. D., Yang, Y. Y., Ouyang, D. S., & Yang, G. P. (2015). A review of biotransformation and pharmacology of ginsenoside compound K. Fitoterapia, 100, 208–220.

    Article  CAS  Google Scholar 

  28. Wang, Y., Choi, K. D., Yu, H., Jin, F., & Im, W. (2016). Production of ginsenoside F1 using commercial enzyme Cellulase KN. Journal of Ginseng Research, 40(2), 121–126.

    Article  Google Scholar 

  29. Luan, H., Qi, L. X., Hu, Y., Hao, D., Cui, Y., & Yang, L. (2006). Purification and characterization of a novel stable ginsenoside Rb1-hydrolyzing β-D-glucosidase from China white jade snail. Process Biochemistry, 41, 1974–1980.

    Article  CAS  Google Scholar 

  30. Du, J., Cui, C. H., Park, S. C., Kim, J. K., Yu, H. S., Jin, F. X., Sun, C. K., Kim, S. C., & Im, W. T. (2014). Identification and characterization of a ginsenoside-transforming β-glucosidase from Pseudonocardia sp. Gsoil 1536 and its application for enhanced production of minor ginsenoside Rg 2 (S). PLoS One, 9, e96914.

    Article  Google Scholar 

  31. Zhang, S. S., Xie, J. C., Zhao, L. G., Pei, J. J., Su, E. Z., Xiao, W., & Wang, Z. Z. (2018). Cloning, overexpression and characterization of a thermostable β-xylosidase from Thermotoga petrophila and cooperated transformation of ginsenoside extract to ginsenoside 20(S)-Rg3 with a β-glucosidase. Bioorganic Chemistry, 85, 159–167.

    Article  Google Scholar 

  32. Treebupachatsakul, T., Nakazawa, H., Shinbo, H., Fujikawa, H., Nagaiwa, A., Ochiai, N., Kawaguchi, T., Nikaido, M., Totani, K., Shioya, K., Shida, Y., Morikawa, Y., Ogasawara, W., & Okada, H. (2016). Heterologously expressed Aspergillus aculeatus β-glucosidase in Saccharomyces cerevisiae is a cost-effective alternative to commercial supplementation of β-glucosidase in industrial ethanol production using Trichoderma reesei cellulases. Journal of Bioscience and Bioengineering, 121, 27–35.

    Article  CAS  Google Scholar 

  33. Kim, M. J., Upadhyaya, J., Yun, M. S., Ryu, N. S., Song, Y. E., Park, H. W., & Kim, M. K. (2017). Highly regioselective biotransformation of ginsenoside Rb2 into compound Y and compound K by β-glycosidase purified from Armillaria mellea mycelia. Journal of Ginseng Research, S1226845317300118.

Download references

Funding

This research was supported by the National Natural Science Foundation of China (21706211, 21576160, 21878246, 21676214), the National Key R&D Program of China (2019YFA0905200) and the Educational Commission of Shaanxi Province of China (16JS104).

Author information

Author notes

  1. JYY and LWN contributed equally to this work.

Authors and Affiliations

  1. Shaanxi Key Laboratory of Degradable Biomedical Materials, School of Chemical Engineering, Northwest University, Taibai North Road 229, Xi’an, 710069, China

    Yunyun Jiang

  2. Shaanxi R&D Center of Biomaterials and Fermentation Engineering, School of Chemical Engineering, Northwest University, Xi’an, 710069, China

    Weina Li

  3. Biotech & Biomed Research Institute, Northwest University, Taibai North Road 229, Xi’an, 710069, Shaanxi, China

    Daidi Fan

Authors
  1. Yunyun Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Weina Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Daidi Fan
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

JYY, LWN, and FDD conceived and designed the study. JYY performed the experiments and analyzed the data. JYY wrote the paper. LWN and FDD reviewed and edited the manuscript. All the authors read and approved the manuscript

Corresponding author

Correspondence to Daidi Fan.

Ethics declarations

This article does not contain any studies with human participants or animals performed by any of the authors.

Conflict of Interest

The authors declare that they have no conflicts of interest.

Additional information

The original online version of this article was revised: Changes has been made to the authors affiliation (article note has been added) and funding.

Supplementary Information

ESM 1

(DOC 1449 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, Y., Li, W. & Fan, D. Biotransformation of Ginsenoside Rb1 to Ginsenoside CK by Strain XD101: a Safe Bioconversion Strategy. Appl Biochem Biotechnol 193, 2110–2127 (2021). https://doi.org/10.1007/s12010-021-03485-0

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12010-021-03485-0

Keywords

Search

Navigation