The present study involves the enantioselective resolution of racemic Felodipine by using free and immobilized forms of microbial cultures as well as an enzyme (Lipase AP6). Among the microbial cultures employed in the present study, Aspergillus niger , Sphingomonas paucimobilis, Cunninghamella elegans, Escherichia coli, Pseudomonas putida and Cunninghamella blakesleeana were found to possess capability of enantioselective resolution of racemic Felodipine. The enantiomeric excess (ee%) of Felodipine after reaction catalyzed by whole-cell A. niger and S. paucimobilis was found as 81.59 and 71.67%, respectively. Immobilization enhanced the enantioselectivity (enantiomeric ratio (E)) of the biocatalysts and hence this led to enhanced enantiomeric purity of the drug. The ee% values were found to be enhanced in reactions catalyzed by A. niger and S. paucimobilis cultures after immobilization as 98.27 and 93.56%, respectively. Enantiomeric ratio (E) of the reactions catalyzed by all the biocatalysts has been improved after immobilization. E value of the reaction catalyzed by immobilized A. niger was found to be excellent (E > 100) and hence the drug showed high enantiomeric purity. In lipase AP6 catalyzed study, the enantioselectivity was enhanced after immobilization with excellent E value, which led to enhanced enantiomeric purity of the drug (99.21% ee%).
Leffingwell, J.C. (2003) Chirality and Bioactivity I. Pharmacology. Leffingwell Reports, 3, 1-27.
Huisman, G.W. and Collier, S.J. (2013) On the Development of New Biocatalytic Processes for Practical Pharmaceutical Synthesis. Current Opinion in Chemical Biology, 17, 284-292. https://doi.org/10.1016/j.cbpa.2013.01.017
Nguyen, L.A., He, H. and Huy, C.P. (2006) Chiral Drugs: An Overview. International Journal of Biomedical Science, 2, 85-100.
Tishkov, V.I. and Zaitseva, E.A. (2008) Modern Trends in Biocatalytic Synthesis of Chiral Compounds. Moscow University Chemistry Bulletin, 63, 111-113. https://doi.org/10.3103/S0027131408020144
Santhosh Kumar, K.P. and Anju, C. (2005) Deracemization of Aromatic β-Hydroxy Esters Using Immobilized Whole Cells of Candida parapsilosis ATCC 7330 and Determination of Absolute Configuration by 1H NMR. Tetrahedron: Asymmetry, 16, 2790-2798. https://doi.org/10.1016/j.tetasy.2005.07.017
Thomson, M.J., Rhys-Williams, W., Hutt, A.J., Lioyd, A.W. and Hanlon, D.W. (1996) Demonstration of the Chiral Inversion of Ibuprofen by Verticillium lecanii in Non-Growing Cultures. Letters in Applied Microbiology, 23, 417-420. https://doi.org/10.1111/j.1472-765X.1996.tb01349.x
Lindmark, B., Ahnoff, M. and Persson, B.A. (2002) Enantioselective Determination of Felodipine in Human Plasma by Chiral Normal-Phase Liquid Chromatography and Electrospray Ionisation Mass Spectrometry. Journal of Pharmaceutical and Biomedical Analysis, 27, 489-495. https://doi.org/10.1016/S0731-7085(01)00582-9
Eltze, M., Boer, R., Sanders, K.H., Boss, H., Ulrich, W.R. and Flocke1rzi, D. (1990) Stereoselective Inhibition of Thromboxane-Induced Coronary Vasoconstriction by 1,4-Dihydropyridine Calcium Channel Antagonists. Chirality, 2, 233-240. https://doi.org/10.1002/chir.530020408
Jin, J.Z., Li, H. and Zhang, J. (2010) Improved Synthesis of (S)-1-Phenyl-2-Propanol in High Concentration with Coupled Whole Cells of Rhodococcus erythropolis and Bacillus subtilis on Preparative Scale. Applied Biochemistry and Biotechnology, 162, 2075-2086. https://doi.org/10.1007/s12010-010-8983-3
Kato, D.I., Miyamoto, K. and Ohta, H. (2005) Preparation of Optically Active 4-Chlorophenylalanine from Its Racemate by Deracemization Technique Using Transformant Escherichia coli Cells. Biocatalysis and Biotransformation, 23, 375-379. https://doi.org/10.1080/10242420500296295
Huang, H.R. and Xu, J.H. (2006) Preparation of (S)-Mandelic Acid from Racemate Using Growing Cells of Pseudomonas putida ECU1009 with R-Mandelate Degradation Activity. Biochemical Engineering Journal, 30, 11-15. https://doi.org/10.1016/j.bej.2006.01.010
Mrutyunjay, S., Andrea, H., Thomas, P., Buser, H.R., Muller, M.D., Charu, D., et al. (2005) Enantioselective Transformation of α-Hexachlorocyclohexane by the Dehydrochlorinases LinA1 and LinA2 from the Soil Bacterium Spingomonas paucimobilis B90A. Applied and Environmental Microbiology, 71, 8514-8518. https://doi.org/10.1128/AEM.71.12.8514-8518.2005
Hirrlinger, B., Stolz, A. and Knackmuss, H.J. (1996) Purification and Properties of an Amidase from Rhodococcus erythropolis MP50 which Enantioselectively Hydrolyzes 2-Arylpropionamides. Journal of Bacteriology, 178, 3501-3507. https://doi.org/10.1128/jb.178.12.3501-3507.1996
Levadoux, W., Trani, M., Lortie, R., Kerr, D. and Groeau, A. (2002) Microbial Resolution of Baclofen by a New Isolate of Streptomyces halstedii. Journal of Bioscience and Bioengineerining, 93, 557-562. https://doi.org/10.1016/S1389-1723(02)80237-7
Da Silva, V.C.F., Contesini, F.J. and Carvalho P.D.O. (2009) Enantioselective Behaviour of Lipases from Aspergillus niger Immobilized in Different Supports. Journal of Industrial Microbiology & Biotechnology, 36, 949-954. https://doi.org/10.1007/s10295-009-0573-4
Damle, S.V., Patil, P.N. and Salunkhe, M. M. (2000) Biotransformations with Rhizopus arrhizus and Geotrichum candidum for the Preparation of (S)-Atenolol and (S)-Propranolol. Bioorganic & Medicinal Chemistry, 8, 2067-2070. https://doi.org/10.1016/S0968-0896(00)00131-0
Comasseto, J.V., Andrade, L.H., Omori, A.T., Assis, L.F. and Meleiro Porto, A.L. (2004) Deracemization of Aryl Ethanols and Reduction of Acetophenones by Whole Fungal Cells of Aspergillus terreus CCT 4083, A. terreus CCT 3320 and Rhizopus oryzae CCT 4964. Journal of Molecular Catalysis B: Enzymatic, 29, 55-61. https://doi.org/10.1016/j.molcatb.2004.01.015
Nie, Y., Xu, Y., Lv, T. F. and Xiao, R. (2009) Enhancement of Candida parapsilosis Catalyzing Deracemization of (R, S)-1-Phenyl-1,2-Ethanediol: Agitation Speed Control during Cell Cultivation. Journal of Chemical Technology and Biotechnology, 84, 468-472. https://doi.org/10.1002/jctb.2070
Barth, T., Conti, R., Pupo, M.T., Okano, L.T. and Bonato, P.S. (2012) Chiral HPLC Analysis of Donepezil, 5-O-Desmethyl Donepezil and 6-O-Desmethyl Donepezil in Culture Medium: Application to Fungal Biotransformation Studies. Analytical and Bioanalytical Chemistry, 404, 257-266. https://doi.org/10.1007/s00216-012-6107-3
Hu, S.H., Tian, X.F. and Han, G.D. (1998) Novel Microbial Hydroxylation of 13-Ethyl-17β-Hydroxy-18, 19-Dinor-17α-Pregn-4-en-20-yn-3-One. Steroids, 63, 88-92. https://doi.org/10.1016/S0039-128X(97)00139-6
Carvalho, P. O., Contesini, F. J. and Ikegaki, M. (2006) Enzymatic Resolution of (R, S)-Ibuprofen and (R, S)-Ketoprofen by Microbial Lipases from Native and Commercial Sources. Brazilian Journal of Microbiology, 37, 329-337. https://doi.org/10.1590/S1517-83822006000300024
Venisetty, R.K., Keshetty, S. and Ciddi, V. (2011) Biotransformation of Silibinin (Silybin) Using Fungal Organisms. Indian Journal of Pharmaceutical Education and Research, 45, 384-391.
Srisailam, K. and Veeresham, C. (2010) Biotransformation of Celecoxib Using Microbial Cultures. Applied Biochemistry and Biotechnology, 160, 2075-2089. https://doi.org/10.1007/s12010-009-8789-3
Pawar, S.V., Meena, V.S., Kaushik, S., Kamble, A., Kumar, S., Chisti, Y. and Banerjee, U.S. (2012) Stereo-Selective Conversion of Mandelonitrile to (R)-(2)-Mandelic Acid Using Immobilized Cells of Recombinant Escherichia coli. Biotech, 2, 319-326.
Venisetty, R.K., Keshetty, S. and Veeresham, C. (2014) Biotransformation of Vincamine Using Microbial Cultures. IOSR Journal of Pharmacy and Biological Sciences, 9, 71-78. https://doi.org/10.9790/3008-09317178
Siódmiak, T., Rumiski, J.K. and Marszall, M.P. (2012) Application of Lipases from Candida rugosa in the Enantioselective Esterification of (R, S)-Ibuprofen. Current Organic Chemistry, 16, 1-6. https://doi.org/10.2174/138527212800194728
Xu, L.F., Lu, Y., Li, Y., and Xu, X. (2010) Comparision of Chiral Separations of Felodipine by High Performance Liquid Chromatography Using Two Celluose tris(4-methybenzoate) Stationary Phases. Chinese Journal of Chromatography, 28, 426-429. https://doi.org/10.3724/SP.J.1123.2012.00426
Faber, K. (2011) Biotransformations in Organic Chemistry. 6th Edition, Springer, Berlin. https://doi.org/10.1007/978-3-642-17393-6
Bhandarkar, S. and Neau, S. (2000) Lipase-Catalyzed Enantioselective Esterification of Flurbiprofen with N-Butanol. Electronic Journal of Biotechnology, 3, 195-201.
Gottemukkala, V.V., Saripella, K.K., Kadari, A.K. and Neau, S.H. (2008) Effect of Methyl branching of C8H18 Alkanes and Water Activity on Lipase Catalyzed Enantioselective Esterification of Ibuprofen. Electronic Journal of Biotechnology, 11, 1-12. https://doi.org/10.2225/vol11-issue1-fulltext-8
Liu, R. (2005) Enzymes as Catalysts in Synthesis of Enantiomerically Pure Building Blocks-Secondary Alcohols Bearing Two Vicinal Stereocentres. PhD Thesis, Kungliga Tekniska Hogskolan (KTH), Stockholm, Sweden.
Pena-Montes, C., Mondragon-Tintor, M.E., Castro-Rodriguez, J.A., Bustos-Jaimes, I., Navarro-Ocaria, A. and Farres, A. (2013) Immobilization and Biochemical Properties of the Enantioselective Recombinant NStcI Esterase of Aspergillus nidulans. Enzyme Research, 2013, Article ID: 928913. https://doi.org/10.1155/2013/928913
Ribeiro J.B., Ramos, A.S., Lopes, R.O., Silva, G.V.V. and Alves de Souza, R. (2014) Whole Cells in Enantioselective Reduction of Benzylacetoacetate. Brazilian Journal of Microbiology, 45, 929-932. https://doi.org/10.1590/S1517-83822014000300023
Tamalampudi, S., Hama, S., Tanino, T., Talukder, M.R., Kondo, A. and Fukuda, H. (2007) Immobilized Recombinant Aspergillus oryzae Expressing Heterologous Lipase: An Efficient Whole-Cell Biocatalyst for Enantioselective Transesterification in Non-Aqueous Medium. Journal of Molecular Catalysis B: Enzymatic, 48, 33-37. https://doi.org/10.1016/j.molcatb.2007.05.007
Hosseinpour, M.N., Najafpour, G.D., Yownsi, H. and Korrami, M. (2011) Submerged Culture Studies for Lipase Production by Aspergillus niger NCIM 584 on Soya Flour. Middle East Journal of Scientific Research, 7, 362-366.
Lee, J.K. and Kim, M.J. (2011) Room Temperature Solid-Phase Ionic Liquid-Immobilized Enzyme for Biocatalysis in Organic Solvent: Markedly Enhanced Enantioselectivity. Bulletin of the Korean Chemical Society, 32, 3149-3151. https://doi.org/10.5012/bkcs.2011.32.8.3149
Alnoch, R.C., Martini, V.P., Glogauer, A., Costa, A.C., Piovan, L., Muller-Santos, M., et al. (2015) Immobilization and Characterization of a New Regioselective and Enantioselective Lipase Obtained from a Metagenomic Library. PLoS ONE, 10, e0114945. https://doi.org/10.1371/journal.pone.0114945