Abstract
20(S)-protopanaxatriol (PPTA), an aglycone of ginseng saponins, is rarely found and is present in a limited amount; it exhibits various pharmaceutical activities, including memory improvement, and anti-diabetic and anti-cancer effects. An enzymatic method was developed to improve 20(S)-protopanaxatriol aglycone [20(S)-PPTA] production using recombinant β-glucosidase (BgpA) cloned from Terrabacter ginsenosidimutans Gsoil 3082T. The optimal hydrolytic activity was obtained at pH 7.0 and 37°C. The enzyme could hydrolyze the rutinoside and glucose moieties at the C6 and C20 positions, respectively, of ginsenosides Re and Rg1 to produce 20(S)-PPTA through the formation of ginsenoside F1 as an intermediate. For gram-scale production, the enzyme reaction was performed in a 10-L fermenter for 48 h at a substrate concentration of 10 mg/mL. Finally, 5.45 g 20(S)-PPTA was produced from 36 g PPT type ginsenoside mixture with 95% purity by chromatography. This study thus reveals an industrial application of a minor component, 20(S)-PPTA.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Dou, D. Q., L. Jin, and Y. J. Chen (1999) Advances and prospects of the study on chemical constituents and pharmacological activities of panax ginseng. J. Shenyang Pharm. Univ. 16: 151–156 (in Chinese).
Popovich, D. G. and D. D. Kitts (2002) Structure-function relationship exists for ginsenosides in reducing cell proliferation and inducing apoptosis in the human leukemia (THP-1) cell line. Arch. Biochem. Biophys. 406: 1–8.
Kobashi, K. and T. Akao (1997) Relation of intestinal bacteria to pharmacological effects of glycosides. Biosci. Microflora. 16: 1–7.
Wang, Y. Z., J. Chen, S. F. Chu, Y. S. Wang, X. Y. Wang, N. H. Chen, and J. T. Zhang (2009) Improvement of memory in mice and increase of hippocampal excitability in rats by ginsenoside Rg1’s metabolites ginsenoside Rh1 and protopanaxatriol}. J. Pharmacol. Sci. 109: 504–510.
Han, K. L., M. H. Jung, J. H. Sohn, and J. K. Hwang (2006) Ginsenoside 20(S)-protopanaxatriol (PPT) activates peroxisome proliferator-activated receptor gamma (PPARgamma ) in 3T3-L1 adipocytes. Biol. Pharm. Bull. 29: 110–113.
Chan, L. Y., H. H. Kwok, R. W. Chan, M. J. Peiris, N. K. Mak, R. N. Wong, M. C. Chan, and P. Y. Yue (2011) Dual functions of ginsenosides in protecting human endothelial cells against influenza H9N2-induced inflammation and apoptosis. J. Ethnopharmacol. 137: 1542–1546.
Kwak, J. H., J. Y. Park, D. Lee, J. Y. Kwak, E. H. Park, K. H. Kim, H. J. Park, H. Y. Kim, H. J. Jang, J. Ham, G. S. Hwang, N. Yamabe, and K. S. Kang (2014) Inhibitory effects of ginseng sapogenins on the proliferation of triple negative breast cancer MDA-MB-231 cells. Bioorg. Med. Chem. Lett. 24: 5409–5412.
Ma, L. Y., Q. L. Zhou, and X. W. Yang (2015) New SIRT1 activator from alkaline hydrolysate of total saponins in the stemsleaves of Panax ginseng. Bioorg. Med. Chem. Lett. 25: 5321–5325.
Liu, G. Y., X. Bu, H. Yan, and W. W. Jia (2007) 20S-protopanaxadiol-induced programmed cell death in glioma cells through caspase-dependent and -independent Pathways. J. Nat. Prod. 70: 259–264.
Lee, B. H., S. H. Hwang, S. H. Choi, H. J. Kim, J. H. Lee, S. M. Lee, Y. G. Ahn, and S. Y. Nah (2013) Inhibitory effects of ginsenoside metabolites, compound K and protopanaxatriol, on GABAC receptor-mediated ion currents. Korean J. Physiol. Pharmacol. 17: 127–132.
Siddiqi M. Z., Z. Aslam, and W. T. Im (2017). Arachidicoccus ginsenosidivorans sp. nov., with ginsenoside converting activity isolated from ginseng cultivating soil. Int. J. Syst. Evol. Microbiol. 67: 1005–1010.
Siddiqi, M. Z., C. H. Cui, S. K. Park, N. S. Han, S. C. Kim, and W. T. Im (2017) Comparative analysis of the expression level of recombinant ginsenoside-transforming β-glucosidase in GRAS hosts and mass production of the ginsenoside Rh2-Mix. PLoS One. 12: e0176098.
Siddiqi, M. Z., S. M. Shafi, and W. T. Im (2017) Complete genome sequencing of Arachidicoccus ginsenosidimutans sp. nov., and its application for production of minor ginsenosides by finding a novel ginsenoside-transforming β-glucosidase. RSC Adv. 7: 46745–46759.
An, D. S., C. H. Cui, M. Z. Siddiqi, H. S. Yu, F. X. Jin, S. G. Kim, and W. T. Im (2017) Gram-scale production of ginsenoside F1 using a recombinant bacterial β-glucosidase. J. Microbiol. Biotechnol. 27: 1559–1565.
Park, C. S., M. H. Yoo, K. H. Noh, and D. K. Oh (2010) Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl. Microbiol. Biotechnol. 87: 9–19.
An, D. S., C. H. Cui, H. G. Lee, L. Wang, S. C. Kim, S. T. Lee, F. Jin, H. Yu, Y. W. Chin, H. K. Lee, W. T. Im, and S. G. Kim (2010) Identification and characterization of a novel Terrabacter ginsenosidimutans sp. nov. β-glucosidase that transforms ginsenoside Rb1 into the rare gypenosides XVII and LXXV. Appl. Environ. Microbiol. 76: 5827–5836.
Wang, Y., K. D. Choi, H. Yu, F. Jin, and W. T. Im (2016) Production of ginsenoside F1 using commercial enzyme Cellulase KN. J. Ginseng Res. 40: 121–126.
Acknowledgments
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2018R1D1A1B07045774); by a grant from the National Institute of Biological Resources (NIBR), funded by the Ministry of Environment (MOE) of the Republic of Korea (NIBR201827103), and by Korea Research Fellowship (KRF) Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and ICT (project no. 2019H1D3A1A02070958).
Author information
Authors and Affiliations
Corresponding author
Additional information
Publisher’s Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
About this article
Cite this article
Siddiqi, M.Z., Jin, M., Song, BK. et al. Enhanced Production of Protopanaxatriol from Ginsenoside Re and Rg1 Using a Recombinant Bacterial β-glucosidase. Biotechnol Bioproc E 24, 632–637 (2019). https://doi.org/10.1007/s12257-019-0090-x
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s12257-019-0090-x