Highly Regioselective Biotransformation of Ginsenoside Rb2 into Compound Y and Compound K by β-glycosidase Purified from Mycelia

Overview

Journal J Ginseng Res

Date 2018 Oct 20

PMID 30337811

Citations 15

Authors

Min-Ji Kim

Jitendra Upadhyaya

Min-Sun Yoon

Nam Soo Ryu

Young Eun Song

Hee-Won Park

Young-Hoi Kim

Myung-Kon Kim

Affiliations

Soon will be listed here.

Abstract

Background: The biological activities of ginseng saponins (ginsenosides) are associated with type, number, and position of sugar moieties linked to aglycone skeletons. Deglycosylated minor ginsenosides are known to be more biologically active than major ginsenosides. Accordingly, the deglycosylation of major ginsenosides can provide the multibioactive effects of ginsenosides. The purpose of this study was to transform ginsenoside Rb2, one of the protopanaxadiol-type major ginsenosides, into minor ginsenosides using β-glycosidase (BG-1) purified from mycelium.

Methods: Ginsenoside Rb2 was hydrolyzed by using BG-1; the hydrolytic properties of Rb2 by BG-1 were also characterized. In addition, the influence of reaction conditions such as reaction time, pH, and temperature, and transformation pathways of Rb2, Rd, F2, compound O (C-O), and C-Y by treatment with BG-1 were investigated.

Results: BG-1 first hydrolyzes 3--outer β-d-glucoside of Rb2, then 3--β-d-glucoside of C-O into C-Y. C-Y was gradually converted into C-K with a prolonged reaction time, but the pathway of Rb2 → Rd → F2 → C-K was not observed. The optimum reaction conditions for C-Y and C-K formation from Rb2 by BG-1 were pH 4.0-4.5, temperature 45-60°C, and reaction time 72-96 h.

Conclusion: β-Glycosidase purified from mycelium can be efficiently used to transform Rb2 into C-Y and C-K. To our best knowledge, this is the first result of transformation from Rb2 into C-Y and C-K by basidiomycete mushroom enzyme.

Citing Articles

Transcriptome Profiling, Cloning, and Characterization of AnGlu04478, a Ginsenoside Hydrolyzing β-Glucosidase from Aspergillus niger NG1306.

Jiang M, Zhu L, Xie S, Ren Z, Chen X, Liu M Curr Microbiol. 2024; 82(1):56.

PMID: 39718650 PMC: 11668888. DOI: 10.1007/s00284-024-04012-0.

Biotransformation approach to produce rare ginsenosides F1, compound Mc1, and Rd2 from major ginsenosides.

Diao M, Chen Y, Meng L, Li J, Xie N Arch Microbiol. 2024; 206(4):176.

PMID: 38493413 DOI: 10.1007/s00203-024-03893-w.

Enzymatic upcycling of wild-simulated ginseng leaves for enhancing biological activities and compound K.

Lim J, Kim H, Kim G, Kim T, Kang C, Kim S Appl Microbiol Biotechnol. 2024; 108(1):207.

PMID: 38353757 PMC: 10866779. DOI: 10.1007/s00253-024-13028-2.

Rare ginsenosides: A unique perspective of ginseng research.

Fan W, Fan L, Wang Z, Mei Y, Liu L, Li L J Adv Res. 2024; 66:303-328.

PMID: 38195040 PMC: 11674801. DOI: 10.1016/j.jare.2024.01.003.

Engineered β-glycosidase from Hyperthermophilic Sulfolobus solfataricus with Improved Rd-hydrolyzing Activity for Ginsenoside Compound K Production.

Fu C, Shen W, Li W, Wang P, Liu L, Dong Y Appl Biochem Biotechnol. 2023; 196(7):3800-3816.

PMID: 37782456 DOI: 10.1007/s12010-023-04745-x.

References

Yu K, Chen F, Li C . Absorption, disposition, and pharmacokinetics of saponins from Chinese medicinal herbs: what do we know and what do we need to know more?. Curr Drug Metab. 2012; 13(5):577-98. DOI: 10.2174/1389200211209050577. View

Yang X, Yang Y, Ouyang D, Yang G . A review of biotransformation and pharmacology of ginsenoside compound K. Fitoterapia. 2014; 100:208-20. DOI: 10.1016/j.fitote.2014.11.019. View

Tawab M, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M . Degradation of ginsenosides in humans after oral administration. Drug Metab Dispos. 2003; 31(8):1065-71. DOI: 10.1124/dmd.31.8.1065. View

Upadhyaya J, Kim M, Kim Y, Ko S, Park H, Kim M . Enzymatic formation of compound-K from ginsenoside Rb1 by enzyme preparation from cultured mycelia of Armillaria mellea. J Ginseng Res. 2016; 40(2):105-12. PMC: 4845050. DOI: 10.1016/j.jgr.2015.05.007. View

Noh K, Oh D . Production of the rare ginsenosides compound K, compound Y, and compound Mc by a thermostable beta-glycosidase from Sulfolobus acidocaldarius. Biol Pharm Bull. 2009; 32(11):1830-5. DOI: 10.1248/bpb.32.1830. View

Quan L, Jin Y, Wang C, Min J, Kim Y, Yang D . Enzymatic transformation of the major ginsenoside Rb2 to minor compound Y and compound K by a ginsenoside-hydrolyzing β-glycosidase from Microbacterium esteraromaticum. J Ind Microbiol Biotechnol. 2012; 39(10):1557-62. DOI: 10.1007/s10295-012-1158-1. View

Park C, Yoo M, Noh K, Oh D . Biotransformation of ginsenosides by hydrolyzing the sugar moieties of ginsenosides using microbial glycosidases. Appl Microbiol Biotechnol. 2010; 87(1):9-19. DOI: 10.1007/s00253-010-2567-6. View

Hasegawa H . 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. 2004; 95(2):153-7. DOI: 10.1254/jphs.fmj04001x4. View

Jin X, Yu H, Wang D, Liu T, Liu C, An D . Kinetics of a cloned special ginsenosidase hydrolyzing 3-O-glucoside of multi-protopanaxadiol-type ginsenosides, named ginsenosidase type III. J Microbiol Biotechnol. 2012; 22(3):343-51. DOI: 10.4014/jmb.1107.07066. View

10.

Christensen L . Ginsenosides chemistry, biosynthesis, analysis, and potential health effects. Adv Food Nutr Res. 2008; 55:1-99. DOI: 10.1016/S1043-4526(08)00401-4. View

11.

Lee G, Kim K, Oh D . Production of rare ginsenosides (compound Mc, compound Y and aglycon protopanaxadiol) by β-glucosidase from Dictyoglomus turgidum that hydrolyzes β-linked, but not α-linked, sugars in ginsenosides. Biotechnol Lett. 2012; 34(9):1679-86. DOI: 10.1007/s10529-012-0949-9. View

12.

Xu Q, Fang X, Chen D . Pharmacokinetics and bioavailability of ginsenoside Rb1 and Rg1 from Panax notoginseng in rats. J Ethnopharmacol. 2003; 84(2-3):187-92. DOI: 10.1016/s0378-8741(02)00317-3. View

13.

Bae E, Park S, Kim D . Constitutive beta-glucosidases hydrolyzing ginsenoside Rb1 and Rb2 from human intestinal bacteria. Biol Pharm Bull. 2001; 23(12):1481-5. DOI: 10.1248/bpb.23.1481. View

14.

Kim W, Kim J, Han S, Lee S, Kim N, Park M . Steaming of ginseng at high temperature enhances biological activity. J Nat Prod. 2001; 63(12):1702-4. DOI: 10.1021/np990152b. View

15.

Kim J, Cui C, Yoon M, Kim S, Im W . Bioconversion of major ginsenosides Rg1 to minor ginsenoside F1 using novel recombinant ginsenoside hydrolyzing glycosidase cloned from Sanguibacter keddieii and enzyme characterization. J Biotechnol. 2012; 161(3):294-301. DOI: 10.1016/j.jbiotec.2012.06.021. View

16.

Wang L, Liu Q, Sung B, An D, Lee H, Kim S . Bioconversion of ginsenosides Rb(1), Rb(2), Rc and Rd by novel β-glucosidase hydrolyzing outer 3-O glycoside from Sphingomonas sp. 2F2: cloning, expression, and enzyme characterization. J Biotechnol. 2011; 156(2):125-33. DOI: 10.1016/j.jbiotec.2011.07.024. View

17.

Lee G, Yoo M, Shin K, Shin K, Kim K, Kim Y . β-glucosidase from Penicillium aculeatum hydrolyzes exo-, 3-O-, and 6-O-β-glucosides but not 20-O-β-glucoside and other glycosides of ginsenosides. Appl Microbiol Biotechnol. 2013; 97(14):6315-24. DOI: 10.1007/s00253-013-4828-7. View

18.

Wong A, Che C, Leung K . Recent advances in ginseng as cancer therapeutics: a functional and mechanistic overview. Nat Prod Rep. 2014; 32(2):256-72. DOI: 10.1039/c4np00080c. View

19.

Yang Hsu B, Jang Lu T, Hui Chen C, Wang S, Hwang L . Biotransformation of ginsenoside Rd in the ginseng extraction residue by fermentation with lingzhi (Ganoderma lucidum). Food Chem. 2013; 141(4):4186-93. DOI: 10.1016/j.foodchem.2013.06.134. View

20.

Chi H, Kim D, Ji G . Transformation of ginsenosides Rb2 and Rc from Panax ginseng by food microorganisms. Biol Pharm Bull. 2005; 28(11):2102-5. DOI: 10.1248/bpb.28.2102. View