Log in

Effect of ionic liquid-containing system on betulinic acid production from betulin biotransformation by cultured Armillaria luteo-virens Sacc cells

  • Original Paper
  • Published:
European Food Research and Technology Aims and scope Submit manuscript

Abstract

The aim of this study is to develop an ionic liquid-containing system for efficient production of betulinic acid by cultured cells Armillaria luteo-virens Sacc ZJUQH100-6. Several parameters affecting betulinic acid formation in the IL-containing system were investigated. The addition of [EMIM][BF4] in hexane-containing reaction medium gave rise to better betulinic acid formation in comparison with other ILs used. The optimal concentration of IL in IL-containing co-solvent system is 50% (v/v). As a co-substrate, butanol is found to be useful for intracellular betulin-28-monooxygenase synthesis during the whole phase. The concentrations of substrate and resting cells have been found to exert a significant effect on betulinic acid. Moreover, the reaction time in this IL-containing system was less than that in the conventional one. The effect of the constructed IL-containing system on cell membrane structure was comparatively observed. Under the developed IL-containing system, the highest yield of product observed was 11.14% at 18 h, higher than that in monophase aqueous one (P < 0.05), whereas the activity of monooxygenase showed the same variation as betulinic acid formation.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

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

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Alakurtti S, Mäkelä T, Koskimies S, Yli-Kauhaluoma J (2006) Pharmacological properties of the ubiquitous natural product betulin. Eur J Pharm Sci 29:1–13

    Article  CAS  Google Scholar 

  2. Yogeeswari P, Sriram D (2005) Betulinic acid and its derivatives: a review on their biological properties. Curr Med Chem 12:657–666

    Article  CAS  Google Scholar 

  3. Mukherjee R, Kumar V, Srivastava SK, Agarwal SK, Burman AC (2006) Betulinic acid derivatives as anticancer agents: structure activity relationship. Anticancer Agents Med Chem 6:271–279

    Article  CAS  Google Scholar 

  4. Pisha E, Chai H, Lee IS, Chagwedera TE, Farnsworth NR, Cordell GA, Beecher CWW, Fong HHS, Kinghorn AD, Brown DM, Wani MC, Wall ME, Hieken TJ, Dasgupta TK, Pezzuto JM (1995) Discovery of betulinic acid as a selective inhibitor of human melanoma that functions by induction of apoptosis. Nat Med 1:1046–1051

    Article  CAS  Google Scholar 

  5. Chatterjee P, Pezzuto JM, Kouzi SA (1999) Glucosidation of betulinic acid by Cunninghamella species. J Nat Prod 62:761–763

    Article  CAS  Google Scholar 

  6. Cichewicz RH, Kouzi SA (2004) Chemistry, biological activity, and chemotherapeutic potential of betulinic acid for the prevention and treatment of cancer and HIV infection. Med Res Rev 35:90–114

    Article  Google Scholar 

  7. Bastos DZL, Pimentel IC, De Jesus DA, De Oliveira BH (2007) Biotransformation of betulinic and betulonic acids by fungi. Phytochemistry 68:834–839

    Article  CAS  Google Scholar 

  8. Borges KB, Borges WD, Duran-Patron R, Pupo MT, Bonato PS, Collado IG (2009) Stereoselective biotransformation using fungi as biocatalysts. Tetrahedron Asymmetr 20:385–397

    Article  CAS  Google Scholar 

  9. Qian LW, Zhang J, Liu JH, Yu BY (2009) Direct microbial-catalyzed asymmetric a-hydroxylation of betulonic acid by Nocardia sp. NRRL 5646. Tetrahedron Lett 50:2193–2195

    Article  CAS  Google Scholar 

  10. Moniruzzaman M, Nakashima K, Kamiya N, Goto M (2010) Recent advances of enzymatic reactions in ionic liquids. Biochem Eng J 48:295–314

    Article  CAS  Google Scholar 

  11. Chen QH, Liu J, Zhang HF, He GQ, Fu ML (2009) The betulinic acid production from betulin through biotransformation by fungi. Enzyme Microb Technol 45:175–180

    Article  CAS  Google Scholar 

  12. Liu J, Fu ML, Chen QH (2011) Biotransformation optimization of betulin into betulinic acid production catalysed by cultured Armillaria luteo-virens Sacc ZJUQH100–6 cells. J Appl Microbiol 101:90–97

    Article  Google Scholar 

  13. Leóna R, Fernandes P, Pinheiro HM, Cabral JMS (1998) Whole-cell biocatalysis in organic media. Enzyme Microb Technol 23:483–500

    Article  Google Scholar 

  14. He JY, Zhou LM, Wang P, Zu L (2009) Microbial reduction of ethyl acetoacetate to ethyl (R)-3-hydroxybutyrate in an ionic liquid containing system. Process Biochem 44:316–321

    Article  CAS  Google Scholar 

  15. Olivier-Bourbigou H, Magna L, Morvan D (2010) Ionic liquids and catalysis: recent progress from knowledge to applications. Appl Catal A Gen 373:1–56

    Article  CAS  Google Scholar 

  16. Park S, Kazlauskas RJ (2003) Biocatalysis in ionic liquids-advantages beyond green technology. Curr Opin Biotechnol 14:432–437

    Article  CAS  Google Scholar 

  17. Erbeldinger M, Mesiano AJ, Russell AJ (2000) Enzymatic catalysis of formation of Z-aspartame in ionic liquid—an alternative to enzymatic catalysis in organic solvents. Biotechnol Prog 16:1129–1131

    Article  CAS  Google Scholar 

  18. Itoh T, Matsushita Y, Abe Y, Han SH, Wada S, Hayase S, Kawatsura M, Takai S, Morimoto M, Hirose Y (2006) Increased enantioselectivity and remarkable acceleration of lipase-catalyzed transesterification by using an imidazolium PEG-alkyl sulfate ionic liquid. Chem Eur J 38:9228–9237

    Article  Google Scholar 

  19. Dhakea KP, Qureshia ZS, Singhalb RS, Bhanagea BM (2009) Candida antarctica lipase B-catalyzed synthesis of acetamides using [BMIm(PF6)] as a reaction medium. Tetrahedron Lett 50:2811–2814

    Article  Google Scholar 

  20. Tian JQ, Wang Q, Zhang ZY (2009) Lipase-catalyzed acylation of l-carnitine with conjugated linoleic acid in [Bmim]PF6 ionic liquid. Eur Food Res Technol 229:357–363

    Article  CAS  Google Scholar 

  21. Cull SG, Holbrey JD, Vargas-Mora V, Seddon KR, Lye GJ (2000) Room-temperature ionic liquids as replacements for organic solvents in multiphase bioprocess operations. Biotechnol Bioeng 69:227–233

    Article  CAS  Google Scholar 

  22. Jain N, Kumar A, Chauhan S, Chauhan SMS (2005) Chemical and biochemical transformations in ionic liquids. Tetrahedron 61:1015–1060

    Article  CAS  Google Scholar 

  23. Moniruzzaman M, Kamiya N, Nakashima K, Goto M, Moniruzzaman M (2008) Water-in-ionic liquid microemulsions as a new medium for enzymatic reactions. Green Chem 10:497–500

    Article  CAS  Google Scholar 

  24. Moniruzzaman M, Kamiya N, Goto A (2009) Biocatalysis in water-in-ionic liquid microemulsions: a case study with horseradish peroxidase. Langmuir 25:977–982

    Article  CAS  Google Scholar 

  25. Matsuda T, Yamagishi Y, Koguchi S, Iwai N, Kitazume T (2006) An effective method to use ionic liquids as reaction media for asymmetric reduction by Geotrichum candidum. Tetrahedron Lett 47:4619–4622

    Article  CAS  Google Scholar 

  26. Carpenter RC, Sotheeswaran S, Sultanbawa MUS, Ternai B (1980) 13C NMR studies of some lupane and taxarane triterpenes. Org Magn Reson 14:462–465

    Article  CAS  Google Scholar 

  27. Kumar AK, Goswami P (2006) Functional characterization of alcohol oxidases from Aspergillus terreus MTCC 6324. Appl Microbiol Biotechnol 72:906–911

    Article  CAS  Google Scholar 

  28. Omura T, Sato R (1964) The carbon monoxide-binding pigment of liver microsomes. Evidence for its hemeprotein nature. J Biol Chem 239:2370–2379

    CAS  Google Scholar 

  29. Lowry OH, Roseborough NJ, Farr AL, Randall RL (1951) Protein measurement with the Folin phenol reagent. J Biol Chem 193:265–275

    CAS  Google Scholar 

  30. Vatsyayana P, Kumara AK, Goswamib P, Goswami P (2008) Broad substrate cytochrome P450 monooxygenase activity in the cells of Aspergillus terreus MTCC 6324. Bioresour Technol 99:68–75

    Article  Google Scholar 

  31. Kabalka GW, Malladi RR (2000) Reduction of aldehydes using trial- kylboranes in ionic liquids. Chem Commun 22:2191–2192

    Article  Google Scholar 

  32. Hernández-Fernández FJ, De los Ríos AP, Rubio M, Gómez D, Víllora G (2007) Enhancement of activity and selectivity in lipase-catalyzed transesterification in ionic liquids by the use of additives. J Chem Technol Biotechnol 82:882–887

    Article  Google Scholar 

  33. Lou WY, Zong MH, Smith TJ (2006) Use of ionic liquids to improve whole-cell biocatalytic asymmetric reduction of acetyltrimethylsilane for efficient synthesis of enantiopure (S)-1-trimethylsilylethanol. Green Chem 8:147–155

    Article  CAS  Google Scholar 

  34. Stewart JD (2000) Organic transformations catalyzed by engineered yeast cells and related systems. Curr Opin Biotechnol 11:363–368

    Article  CAS  Google Scholar 

  35. Yang W, Jiang T, Acosta D, Davis PJ (1993) Microbial models of mammalian metabolism: involvement of cytochrome P450 in the N-demethylation of N-metheybazole by Cunninghamella echinulata. Xenobiotica 23:973–982

    Article  CAS  Google Scholar 

  36. Zhang D, Hansen EB Jr, Deck J, Heinze TM, Henderson A, Korfmacher WA, Cerniglia CE (1997) Fungal transformations of antihistamines: metabolism of cyproheptadine hydrochloride by Cunninghamella elegans. Xenobiotica 27:301–315

    Article  CAS  Google Scholar 

  37. Contesini FJ, De Carvalho PO (2006) Esterification of (RS)-Ibuprofen by native and commercial lipases in a two-phase system containing ionic liquids. Tetrahedron Asymmetr 17:2069–2073

    Article  CAS  Google Scholar 

  38. Brautigam S, Bringer-Meyer S, Weuster-Botz D (2007) Asymmetric whole cell biotransformation in biphasic ionic liquid/water-systems by use of recombinant Escherichia coli with intracellular cofactor regeneration. Tetrahedron Asymmetr 18:1883–1887

    Article  Google Scholar 

  39. Lenourry A, Gardiner JM, Stephens G (2005) Hydrogenation of C–C double bonds in an ionic liquid reaction system using the obligate anaerobe, Sporomusa termitida. Biotechnol Lett 27:161–165

    Article  CAS  Google Scholar 

  40. Halling PJ (1994) Thermodynamic predictions for biocatalysis in nonconventional media: theory, tests, and recommendations for experimental-design and analysis. Enzyme Microb Technol 16:178–206

    Article  CAS  Google Scholar 

  41. Zehentgruber D, Drǎgan CA, Bureik M, Lütz S (2010) Challenges of steroid biotransformation with human cytochrome P450 monooxygenase CYP21 using resting cells of recombinant Schizosaccharomyces pombe. J Biotechnol 146:179–185

    Article  CAS  Google Scholar 

  42. Eckstein M, Sesing M, Kragl U, Adlercreutz P (2002) At low water activity α-chymotrypsin is more active in an ionic liquid than in non-ionic organic solvents. Biotechnol Lett 24:867–872

    Article  CAS  Google Scholar 

  43. Lou WY, Chen L, Zhang BB, Smith TJ, Zong MH (2009) Using a water-immiscible ionic liquid to improve asymmetric reduction of 4-(trimethylsilyl)-3-butyn-2-one catalyzed by immobilized Candida parapsilosis CCTCC M203011 cells. BMC Biotechnol 9:90

    Article  Google Scholar 

Download references

Acknowledgments

This work was financially supported by the National Natural Science Foundation of China (No. 20806069).

Author information

Authors and Affiliations

Authors

Corresponding authors

Correspondence to Chen Qi-he or Liu **ao-jie.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ming-liang, F., **g, L., Ya-chen, D. et al. Effect of ionic liquid-containing system on betulinic acid production from betulin biotransformation by cultured Armillaria luteo-virens Sacc cells. Eur Food Res Technol 233, 507–515 (2011). https://doi.org/10.1007/s00217-011-1549-y

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00217-011-1549-y

Keywords

Navigation