Immobilization of Candida rugosa lipase for resolution of racimic ibuprofen

Abstract

Aim

Due to lipases’ regio-selectivity and ability to catalyze different reactions such as hydrolysis, esterification, and transesterification, the enzyme is attractive in biotransformation technology. Besides, another technology, namely enzyme immobilization, has attracted scientists/technologists’ attention to employ immobilized lipase in such a field. Thus lipase of Candida rugosa was immobilized onto silica nanoparticles through adsorption. Furthermore, the immobilized biocatalyst was characterized and used to esterify ibuprofen enantioselectively.

Methods

To characterize immobilized lipase onto silica nanoparticles scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used.

Results

The catalytic properties of both immobilized and free lipases such as optima pH and temperature were not different. According to the results, the immobilized lipase on silica nanoparticles showed 45% and 96% conversion (C) and enantioselectivity (ees), respectively. In comparison to free lipase, the immobilized enzyme came with better catalytic activity.

Conclusion

Silica nanoparticles as one of the most promising materials for the immobilization of lipase in enantioselective esterification of ibuprofen, were introduced in this work.

Graphical abstract

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References

  1. 1.

    Xie Y-C, Liu H-Z, Chen J-Y. Candida rugosa lipase catalyzed esterification of racemic ibuprofen with butanol: racemization of R-ibuprofen and chemical hydrolysis of S-ester formed. Biotechnology Letters. 1998;20:455–8.

    CAS  Article  Google Scholar 

  2. 2.

    Shoda SI, Uyama H, Kadokawa JI, Kimura S, Kobayashi S. Enzymes as green catalysts for precision macromolecular synthesis. Chemical Reviews. 2016;116:2307–413.

    CAS  Article  Google Scholar 

  3. 3.

    Sie Yon L, Gonawan FN, Kamaruddin AH, Uzir MH. Enzymatic deracemization of (R, S)-ibuprofen ester via lipase-catalyzed membrane reactor. Ind Eng Chem Res. 2013;52:9441–53.

    CAS  Article  Google Scholar 

  4. 4.

    Muralidhar RV, Marchant R, Nigam P. Lipases in racemic resolutions. Journal of Chemical Technology & Biotechnology: International Research in Process, Environmental & Clean Technology. 2001;76:3–8.

    CAS  Article  Google Scholar 

  5. 5.

    Bayramoğlu G, Arıca MY. Preparation of poly (glycidylmethacrylate–methylmethacrylate) magnetic beads: application in lipase immobilization. J Mol Catal B Enzym. 2008;55:76–83.

    Article  Google Scholar 

  6. 6.

    Yahya AR, Anderson WA, Moo-Young M. Ester synthesis in lipase-catalyzed reactions. Enzyme and Microbial Technology. 1998;23:438–50.

    CAS  Article  Google Scholar 

  7. 7.

    Carvalho PDO, Contesini FJ, Ikegaki M. Enzymatic resolution of (R, S)-ibuprofen and (R, S)-ketoprofen by microbial lipases from native and commercial sources. Brazilian Journal of Microbiology. 2006;37:329–37.

    CAS  Article  Google Scholar 

  8. 8.

    Ghanem A. Direct enantioselective HPLC monitoring of lipase-catalyzed kinetic resolution of flurbiprofen. Chirality. 2010;22:597–603.

    CAS  PubMed  Google Scholar 

  9. 9.

    Liu Y, Wang F, Tan T. Effects of alcohol and solvent on the performance of lipase from Candida sp. in enantioselective esterification of racemic ibuprofen. J Mol Catal B Enzym. 2009;56:126–30.

    CAS  Article  Google Scholar 

  10. 10.

    Burney PR, Pfaendtner J. Structural and dynamic features of Candida rugosa lipase 1 in water, octane, toluene, and ionic liquids BMIM-PF6 and BMIM-NO3. J Phys Chem B. 2013;117:2662–70.

    CAS  Article  Google Scholar 

  11. 11.

    Sánchez A, Valero F, Lafuente J, Solà C. Highly enantioselective esterification of racemic ibuprofen in a packed bed reactor using immobilised Rhizomucor miehei lipase. Enzyme and Microbial Technology. 2000;27:157–66.

    Article  Google Scholar 

  12. 12.

    Kato K, Gong Y, Saito T, Kimoto H. Efficient preparation of optically active ketoprofen by Mucor javanicus lipase immobilized on an inorganic support. J Biosci Bioeng. 2000;90:332–4.

    CAS  Article  Google Scholar 

  13. 13.

    Morrone R, D’Antona N, Lambusta D, Nicolosi G. Biocatalyzed irreversible esterification in the preparation of S-naproxen. Journal of molecular catalysis B: Enzymatic. 2010;65:49–51.

    CAS  Article  Google Scholar 

  14. 14.

    Pinnen F, Sozio P, Cacciatore I, Cornacchia C, Mollica A, et al. Ibuprofen and glutathione conjugate as a potential therapeutic agent for treating Alzheimer's disease. Archiv der Pharmazie. 2011;344:139–48.

    CAS  Article  Google Scholar 

  15. 15.

    Madhav MV, Ching CB. Study on the enzymatic hydrolysis of racemic methyl ibuprofen ester. Journal of Chemical Technology & Biotechnology. 2001;76:941–8.

    CAS  Article  Google Scholar 

  16. 16.

    Zhao X-G, Wei D-Z, Song Q-X. A facile enzymatic process for the preparation of ibuprofen ester prodrug in organic media. Journal of Molecular Catalysis B: Enzymatic. 2005;36:47–53.

    CAS  Article  Google Scholar 

  17. 17.

    Chen JC, Tsai SW. Enantioselective synthesis of (S)-ibuprofen ester prodrug in cyclohexane by Candida rugosa lipase immobilized on Accurel MP1000. Biotechnology progress. 2000;16:986–92.

    CAS  Article  Google Scholar 

  18. 18.

    Long WS, Kow PC, Kamaruddin AH, Bhatia S. Comparison of kinetic resolution between two racemic ibuprofen esters in an enzymic membrane reactor. Process Biochemistry. 2005;40:2417–25.

    CAS  Article  Google Scholar 

  19. 19.

    Tsai SW, Lin JJ, Chang CS, Chen JP. Enzymatic synthesis of (S)-ibuprofen ester prodrug from racemic ibuprofen by lipase in organic solvents. Biotechnology Progress. 1997;13:82–8.

    CAS  Article  Google Scholar 

  20. 20.

    Mazaleuskaya LL, Theken KN, Gong L, Thorn CF, FitzGerald GA, Altman RB, et al. PharmGKB summary: ibuprofen pathways. Pharmacogenet Genomics. 2015;25(2):96–106.

    CAS  Article  Google Scholar 

  21. 21.

    Fazlena H, Kamaruddin A, Zulkali M. Dynamic kinetic resolution: alternative approach in optimizing S-ibuprofen production. Bioprocess and Biosystems Engineering. 2006;28:227–33.

    CAS  Article  Google Scholar 

  22. 22.

    Foresti ML, Galle M, Ferreira ML, Briand LE. Enantioselective esterification of ibuprofen with ethanol as reactant and solvent catalyzed by immobilized lipase: experimental and molecular modeling aspects. Journal of Chemical Technology & Biotechnology. 2009;84:1461–73.

    CAS  Article  Google Scholar 

  23. 23.

    Cao S-L, Huang Y-M, Li X-H, et al. Preparation and characterization of immobilized lipase from Pseudomonas cepacia onto magnetic cellulose nanocrystals. Scientific reports. 2016;6:20420.

    CAS  Article  Google Scholar 

  24. 24.

    da Silva VCF, Contesini FJ, de Oliveira Carvalho P. Enantioselective behavior of lipases from Aspergillus niger immobilized in different supports. Journal of Industrial Microbiology & Biotechnology. 2009;36:949–54.

    CAS  Article  Google Scholar 

  25. 25.

    Liu X, Guan Y, Shen R, Liu H. Immobilization of lipase onto micron-size magnetic beads. J Chromatogr B. 2005;822:91–7.

    CAS  Article  Google Scholar 

  26. 26.

    Jiang Y, Guo C, Xia H, Mahmood I, Liu C, Liu H. Magnetic nanoparticles supported ionic liquids for lipase immobilization: Enzyme activity in catalyzing esterification. Journal of Molecular Catalysis B: Enzymatic. 2009;58:103–9.

    CAS  Article  Google Scholar 

  27. 27.

    Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Analytical Biochemistry. 1976;72:248–54.

    CAS  Article  Google Scholar 

  28. 28.

    Kruger NJ. The Bradford method for protein quantitation, The protein protocols handbook, Springer. 2009; pp. 17–24.

  29. 29.

    Guo J, Chen C-P, Wang S-G, Huang X-J. A convenient test for lipase activity in aqueous-based solutions. Enzyme Microb Technol. 2015;71:8–12.

  30. 30.

    López N, Pernas MA, Pastrana LM, Sánchez A, Valero F, Rúa ML. Reactivity of pure Candida rugosa lipase isoenzymes (Lip1, Lip2, and Lip3) in aqueous and organic media. Influence of the isoenzymatic profile on the lipase performance in organic media. Biotechnology Progress. 2004;20:65–73.

    Article  Google Scholar 

  31. 31.

    Serra E, Mayoral Á, Sakamoto Y, Blanco RM, Díaz I. Immobilization of lipase in ordered mesoporous materials: Effect of textural and structural parameters. Microporous and Mesoporous Materials. 2008;114:201–13.

    CAS  Article  Google Scholar 

  32. 32.

    Hermanova S, Zarevucka M, Bousa D, Pumera M, Sofer Z. Graphene oxide immobilized enzymes show high thermal and solvent stability. Nanoscale. 2015;7:5852–8.

    CAS  Article  Google Scholar 

  33. 33.

    Sagiroglu A, Klinnc A, Telefoncu A. Preparation and properties of lipases immobilized on different supports. Artificial cells and blood substitute. Biotechnology. 2004;32(4):625–36.

    CAS  Google Scholar 

  34. 34.

    Dasilva VF, Contesini FJ, de O. Carvalho P. Characterization and catalytic activity of free and immobilized lipase from Aspergilus niger :a comparitive study. J. Braz. Chem. Soc. 2008;1998:1468–74.

    Google Scholar 

  35. 35.

    Wu SH, Guo ZW, Sih CJ. Enhancing the enantioselectivity of Candida lipase-catalyzed ester hydrolysis via noncovalent enzyme modification. Journal of American Chemical Society. 1990;112:1990–5.

    CAS  Article  Google Scholar 

  36. 36.

    Mustranta A. Use of lipases in the resolution of racemic ibuprofen. Applied Microbiology and Biotechnology. 1992;38:61–6.

    CAS  Article  Google Scholar 

  37. 37.

    Goto M, Kamiya N, Miyata M, Nakashio F. Enzymatic esterification by surfactant-coated lipase in organic media. Biotechnology Progress. 1994;10:263–8.

    CAS  Article  Google Scholar 

  38. 38.

    Hongwei Y, Jinchuan W, Chi Bun C. Kinetic resolution of ibuprofen catalyzed by Candida rugosa lipase in ionic liquids. Chirality. 2005;17:16–21.

    Article  Google Scholar 

  39. 39.

    Li K, Wang J, He Y, Cui G, Abdulrazaq MA, Yan Y. Enhancing enzyme activity and enantioselectivity of Burkholderia cepacia lipase via immobilization on melamine-glutaraldehyde dendrimer modified magnetic nanoparticles. Chemical Engineering Journal. 2018;351:258–68.

    CAS  Article  Google Scholar 

  40. 40.

    Swetha E, Vijitha C, Veeresham C. Enantioselective conversion of racemic Sotalol to R(−)-Sotalol by lipase AP6. Indian Journal of Pharmaceutical Sciences. 2018;80(4):676–85.

    CAS  Article  Google Scholar 

  41. 41.

    Xu L, Cui G, Ke C, Fan Y, Yan Y. Immobilized Burkholderia cepacia Lipase on pH-Responsive Pullulan Derivatives with Improved Enantioselectivity in Chiral Resolution. Catalysts. 2018;8(1):13.

    Article  Google Scholar 

  42. 42.

    Gilani SL, Najafpour GD, Heydarzadeh HD, Moghadamnia A. Enantioselective synthesis of (S)-naproxen using immobilizedlipase on chitosan beads. Chirality. 2017;29:304–14.

    CAS  Article  Google Scholar 

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Acknowledgments

The authors acknowledge the technical support of the Department of Biochemistry, Tehran University of Medical Sciences.

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Correspondence to Dariush Norouzian.

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Ghofrani, S., Allameh, A., Yaghmaei, P. et al. Immobilization of Candida rugosa lipase for resolution of racimic ibuprofen. DARU J Pharm Sci (2021). https://doi.org/10.1007/s40199-021-00388-7

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Keywords

  • Lipase
  • Characterization esterification
  • Enantiomeric resolution