High-Yield Biocatalysis of Baicalein 7-O-β-d-Glucuronide to Baicalein Using Soluble Helix pomatia-Derived β-Glucuronidase in a Chemically Defined Acidic Medium

  • Cahit MuderrisogluEmail author
  • Ozlem Yesil-CeliktasEmail author


Baicalein, showing stronger pharmacological activity, can be obtained by removal of the distal glucuronic acid (GluA) from baicalein 7-O-β-D-glucuronide (baicalin). In the present study, a chemically defined reaction medium comprised of mildly acidic (pH 4.5, 37 °C) aqueous solution, was formulated for biotransformation of baicalin to baicalein using acidic Helix pomatia derived beta-glucuronidase (HP-GUS), an untested biocatalyst source. The biotransformation was carried out as a batchwise process within an optimised reaction cocktail (with 5% dimethylformamide, v/v) by a 4-h HP-GUS (250 unit/ml) incubation of baicalin (60 ppm) and resulted in a promising conversion ratio of 99% without any by-product formation. The formulated reaction system may offer a novel and efficient alternative for bioproduction of baicalein, which can be vital for pharmaceutical applications.

Graphical Abstract


Biotransformation Scutellaria baicalensis Georgi Baicalin Baicalein β-Glucuronidase 



The financial support provided by the Scientific and Technological Research Council of Turkey (TUBITAK, 113M050) is highly appreciated. Special thanks to Dr Ismail Hakki Akgun from Ege University Bioengineering Department for his guidance as to UPLC analysis of the reaction samples.

Compliance with Ethical Standards

Conflict of interest

The authors have no conflicts of interest in relation to the manuscript.

Supplementary material

10562_2019_2745_MOESM1_ESM.docx (507 kb)
Supplementary material 1 (DOCX 506 KB)


  1. 1.
    Kitamura K, Honda M, Yoshizaki H, Yamamoto S, Nakane H, Fukushima M, Ono K, Tokunaga T (1998) Antiviral Res 37:131CrossRefGoogle Scholar
  2. 2.
    Chen S, Ruan Q, Bedner E, Deptala A, Wang X, Hsieh TC, Traganos F, Darzynkiewicz Z (2001) Cell Prolif 34:293CrossRefGoogle Scholar
  3. 3.
    Kim HP, Son KH, Chang HW, Kang SS (2004) J Pharmacol Sci 96:229CrossRefGoogle Scholar
  4. 4.
    Chen H, Gao Y, Wu J, Chen Y, Chen B, Hu J, Zhou J (2014) Cancer Lett 354:5CrossRefGoogle Scholar
  5. 5.
    Srinivas NR (2010) Xenobiotica 40:357CrossRefGoogle Scholar
  6. 6.
    Zhang Y, Wu H, Li L, Li J, Jiang Z, Jiang Y, Chen Y (2009) J Mol Catal B 57:130CrossRefGoogle Scholar
  7. 7.
    Jiang Z, Zhang Y, Li J, Jiang W, Yang D, Wu H (2007) Ind Eng Chem Res 46:1883CrossRefGoogle Scholar
  8. 8.
    Huang HZ, Feng B, Song XB, Ma BP (2011) Biocatal Biotransform 29:179CrossRefGoogle Scholar
  9. 9.
    Dong LL, Fu YJ, Zu YG, Luo M, Wang W, Li XJ, Li J (2012) Food Chem 131:1422CrossRefGoogle Scholar
  10. 10.
    Ku S, Zheng H, Park MS, Ji GE (2011) J Korean Soc Appl Biol Chem 54:275CrossRefGoogle Scholar
  11. 11.
    Yang X, Liu L, Wang L, Chen F, Shen M, Pu J (2015) J Xi’an Polytech Univ 1:12Google Scholar
  12. 12.
    Zhao Q, Chen XY, Martin C (2016) Sci Bull 61:1391CrossRefGoogle Scholar
  13. 13.
    Li J, Jiang Z, Wu H, Long L, Jiang Y, Zhang L (2009) Compos Sci Technol 69:539CrossRefGoogle Scholar
  14. 14.
    Li L, Jiang Z, Wu H, Feng Y, Li J (2009) Mater Sci Eng C 29:2029Google Scholar
  15. 15.
    Song X, Jiang Z, Li L, Wu H (2014) Front Chem Sci Eng 8:353CrossRefGoogle Scholar
  16. 16.
    Zhang Y, Wu H, Li J, Li L, Jiang Y, Jiang Y, Jiang Z (2008) Chem Mater 20:1041CrossRefGoogle Scholar
  17. 17.
    Qiu F, Tang X, He ZG, Li HZ (2004) J Chin Pharma Sci 13:134Google Scholar
  18. 18.
    Ou S, Wang S, Zhang H, Zheng Q, Liu H, Yang M (2009) Prog Mod Biomed 9:3954Google Scholar
  19. 19.
    Yoshizuka K, Ohta H, Inoue K, Kitazaki H, Ishimaru M (1996) J Membr Sci 118:41CrossRefGoogle Scholar
  20. 20.
    Beta glucuronidase from Helix pomatia, G7017 Accessed 2 Feb 2018
  21. 21.
    Xing J, Chen X, Zhong D (2005) J Pharma Biomed Anal 39:593CrossRefGoogle Scholar
  22. 22.
    Wu H, Long X, Yuan F, Chen L, Pan S, Liu Y, Stowell Y, Li X (2014) Acta Pharmaceutica Sinica B 4:217CrossRefGoogle Scholar
  23. 23.
    Baicalein, Product Information Accessed 2 Oct 2017
  24. 24.
    Gao WY, Deng YY (2005) Chinese Patent CN 1594305 AGoogle Scholar
  25. 25.
    Ohkoshi E, Nagashima T, Sato H, Fujii Y, Nozawa K, Nagai M (2009) J Chromatogr A 1216:2192CrossRefGoogle Scholar
  26. 26.
    Liu H, Dong Y, Gao Y, Du Z, Wang Y, Cheng P, Chen A, Huang H (2016) Int J Mol Sci 17:1681CrossRefGoogle Scholar
  27. 27.
    Ciesielska E, Wolszczak M, Gulanowski B, Szulawska A, Kochman A, Metodiewa D (2004) In Vivo 18:497Google Scholar
  28. 28.
    Wang CZ, Zhang CF, Chen L, Anderson S, Lu F, Yuan CS (2015) Int J Oncol 47:1749CrossRefGoogle Scholar
  29. 29.
    Liang R, Han RM, Fu LM, Ai XC, Zhang JP, Skibsted LH (2009) J Agric Food Chem 57:7118CrossRefGoogle Scholar
  30. 30.
  31. 31.
    Sun H, Zhang L, Chow ECY, Lin G, Zuo Z, Pang KS (2008) J Pharmacol Exp Ther 326:117CrossRefGoogle Scholar
  32. 32.
    Liang R, Chen C, Ai X, Zhang J (2010) Chin J Magnetic Resonance 27:132Google Scholar
  33. 33.
    Baicalin Product Information. Accessed 21 Sep 2017
  34. 34.
    Kamal MZ, Yedavalli P, Deshmukh MV, Rao NM (2013) Protein Sci 22:904CrossRefGoogle Scholar
  35. 35.
    Szabelski M, Stachowiak K, Wiczk W (2001) Acta Biochim Pol 48:1197Google Scholar
  36. 36.
    Muderrisoglu C, Saveleva M, Abalymov A, Van der Meeren L, Ivanova A, Atkin V, Parakhonskiy B, Skirtach AG (2018) Adv Mater Interfaces 5:1800452CrossRefGoogle Scholar
  37. 37.
    Ding X, Zhang XD, Dong CL, Guan Z, He YH (2018) Catal Lett 148:757CrossRefGoogle Scholar
  38. 38.
    Meng LJ, Liu YY, Zhou HS, Yin XJ, Wu JP, Wu MB, Xu G, Yang LR (2018) Catal Lett 148:3309CrossRefGoogle Scholar
  39. 39.
    Muderrisoglu C, Sargin S, Yesil-Celiktas O (2018) Biotechnol Lett 40:773CrossRefGoogle Scholar
  40. 40.
    Robinson PK (2015) Essays Biochem 59:1CrossRefGoogle Scholar
  41. 41.
    Janseen AE, Van der Padt A, Van Sonsbeek HM, Van’t Riet K (1993) Biotechnol Bioeng 41:95CrossRefGoogle Scholar
  42. 42.
    Zapata-Torres G, Fierro A, Miranda-Rojas S, Guajardo C, Saez-Briones P, Salgado JC, Celis-Barros C (2012) J Chem Inf Model 52:1213CrossRefGoogle Scholar
  43. 43.
    Mesa M, Pereañez JA, Preciado LM, Bernal C (2018) Int J Biol Macromol 120:2410CrossRefGoogle Scholar
  44. 44.
    Mohan C, Long K, Mutneja M, EMD Millipore Corp (2013) 3–13Google Scholar
  45. 45.
    Miletić N, Nastasović A, Loos K (2012) Biores Technol 115:126CrossRefGoogle Scholar
  46. 46.
    β-Glucuronidase from Escherichia coli, recombinant from overexpressing Escherichia coli BL21 Accessed 10 Dec 2018
  47. 47.
    Yildiz-Ozturk E, Yucel M, Muderrisoglu C, Sargin S, Yesil-Celiktas O (2017) J Taiwan Inst Chem Eng 80:100CrossRefGoogle Scholar

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© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Bioengineering, Faculty of EngineeringEge UniversityBornova, IzmirTurkey

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