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Microbial biotransformation: a tool for drug designing

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Abstract

For centuries microbial biotransformation has proved to be an imperative tool in alleviating the production of various chemicals used in food, pharmaceutical, agrochemical and other industries. In the field of pharmaceutical research and development, biotransformation studies have been extensively applied to investigate the metabolism of compounds (leads, lead candidates, etc.) using animal models. The microbial biotransformation phenomenon is then commonly employed in comparing metabolic pathways of drugs and scaling up the metabolites of interest discovered in these animal models for further pharmacological and toxicological evaluation. Microorganisms can conveniently afford drugs difficult obtained via synthesis. The plethora of reported microbial biotransformations along with its added benefits has already invoked further research in bioconversion of novel and structurally complex drugs. This review alternatively discusses the prospect of microbial biotransformation studies as a significant element ameliorating drug discovery and design in terms of cost-effectiveness, environment protection and greater structural diversity as compared to animal models used to study metabolism. To explicate the microbial biotransformation paradigm in drug designing 3 main areas in this aspect have been analyzed: 1—lead expansion: obtaining pharmacologically improved metabolites from bioactive molecules; 2—biosynthesis of precursors/intermediates involved in the production of bioactive molecules; 3—resolution of racemic mixture to obtain enantiomers possessing different pharmacological profiles.

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References

  1. Venisetty, R.K. and Ciddi, V., Curr. Pharm. Biotechnol., 2003, vol. 4, no. 3, pp. 153–167.

    Article  PubMed  CAS  Google Scholar 

  2. Fura, A., Drug Discov. Today, 2006, vol. 11, nos. 3/4, pp. 133–141.

    Article  PubMed  CAS  Google Scholar 

  3. Leuenberger, H.G.W., Pure Appl. Chem., 1990, vol. 62, pp. 753–768.

    Article  CAS  Google Scholar 

  4. Newman, D.J., Cragg, G.M., and Snader, K.M., Nat. Prod. Rep., 2000, vol. 17, no. 3, pp. 215–234.

    Article  PubMed  CAS  Google Scholar 

  5. Rathbone, D.A. and Bruce, N.C., Curr. Opin. Microbiol., 2002, vol. 5, no. 3, pp. 274–281.

    Article  PubMed  CAS  Google Scholar 

  6. El Sayed, K., J. Nat. Prod., 1998, vol. 61, no. 1, pp. 149–151.

    Article  PubMed  Google Scholar 

  7. Orabi, K.Y., Li E., Clark, A.M., and Hufford, C.D., J. Nat. Prod., 1999, vol. 62, no. 7, pp. 988–992.

    Article  PubMed  CAS  Google Scholar 

  8. El Sayed, K.A., Phytochemistry, 2000, vol. 53, no. 6, pp. 675–678.

    Article  PubMed  Google Scholar 

  9. Bister-Miel, F., Agier, C., Bury, M., Postaire, E., Guignard, J. L., and Viel, C., Plant Med. Phytother., 1986, vol. 20, no.1, pp. 3–7.

    CAS  Google Scholar 

  10. Christinaki, H., Bister-Miel, F., Hammoumi, A., Bury, M., Guignard, J. L., and Viel, C., Phytochemistry, 1987, vol. 26, no.11, pp. 2991–2994.

    Article  CAS  Google Scholar 

  11. Dorisse, P., Gleye, J., Loiseau, P., Puig, P., Edy, A. M., and Henry, M., J. Nat. Prod., 1988, vol. 51, no. 3, pp. 532–536.

    Article  PubMed  CAS  Google Scholar 

  12. Rideau, M., Morard, P., Gansser, C., Chenieux, J. C., and Viel, C., Pharmazie, 1988, vol. 43, no. 5, pp.332–334.

    CAS  Google Scholar 

  13. Herath, W., Mikell, J.R., Ferreira, D., and Khan, I.A., Chem. Pharm. Bull., 2003, vol. 51, no. 6, pp. 646–648.

    Article  PubMed  CAS  Google Scholar 

  14. Nogawa, T., Kamano, Y., Yamashita, A., and Pettit, G.R., J. Nat. Prod., 2001, vol. 64, no. 9, pp. 1148–1152.

    Article  PubMed  CAS  Google Scholar 

  15. Yeh, J.Y., Huang, W.J., Kan, S.F., and Wang, P.S., Prostate, 2003, vol. 54, no. 2, pp. 112–124.

    Article  PubMed  CAS  Google Scholar 

  16. Kamano, Y., Kotake, A., Hashima, H., Inoue, M., Morita, H., Takeya, et al., Bioorg. Med. Chem., 1998, vol. 6, no. 7, pp. 1103–1115.

    Article  PubMed  CAS  Google Scholar 

  17. Kamano, Y., Yamashita, A., Nogawa, T., Morita, H., Takeya, K., Itokawa, H. et al., J. Med. Chem., 2002, vol. 45, no. 25, pp. 5440–5447.

    Article  PubMed  CAS  Google Scholar 

  18. Ye, M., Qu, G., Guo, H., and Guo, D., J. Steroid. Biochem. Mol. Biol., 2004, vol. 91, nos. 1–2, pp. 87–98.

    Article  PubMed  CAS  Google Scholar 

  19. Zhang, J., Sun, Y., Liu, J.H., Yu, B.Y., and Xu, Q., Bioorg. Med. Chem., 2007, vol. 17, no. 22, pp. 6062–6065.

    Article  CAS  Google Scholar 

  20. Porto, T.S., Rangel, R., Furtado, N.A.J.C., De Carvalho, T.C., Martins, C.H.G., Veneziani, R.C.S., et al., Molecules, 2009, vol. 14, no. 1, pp.191–199.

    Article  PubMed  CAS  Google Scholar 

  21. Severiano, M.E., Simão, M.R., Porto, T.S., Martins, C.H., Veneziani, R.C., Furtado, et al., Molecules, 2010, vol. 15, no. 12, pp. 8553–8566.

    Article  PubMed  CAS  Google Scholar 

  22. Urzúa, A., Rezende, M.C., Mascayano, C., and Vasquez, L., Molecules, 2008, vol. 13, no. 4, pp. 882–891.

    Article  PubMed  Google Scholar 

  23. Parshikov, I.A., Miriyala, B., Muraleedharan, K.M., Avery, M.A., and Williamson, J.S., J. Ind. Microbiol. Biotechnol., 2006, vol. 33, no. 5, pp. 349–352.

    Article  PubMed  CAS  Google Scholar 

  24. Parshikov, I.A., Miriyala, B., Avery, M.A., and Williamson, J.S., Biotechnol. Lett., 2004, vol. 26, no. 7, pp. 607–610.

    Article  PubMed  CAS  Google Scholar 

  25. Yagi, A., Uemura, T., Okamura, N., Haraguchi, H., Imoto, T., and Hashimoto, K., Phytochemistry, 1997, vol. 35, no. 4, pp. 885–887.

    Article  Google Scholar 

  26. Haraguchi, H., Ohmi, I., Sakai, S., Fukluda, A., Toihara, Y., Fujimoto, T., et al., J. Nat. Prod., 1996, vol. 59, pp. 443–445.

    Article  PubMed  CAS  Google Scholar 

  27. Ibrahim, A.R., Phytochemistry, 2000, vol. 53, no. 2, pp. 209–212.

    Article  PubMed  CAS  Google Scholar 

  28. Ibrahim, A.R., Chem. Pharm. Bull., 2005, vol. 53, no. 6, pp.671–673.

    Article  PubMed  CAS  Google Scholar 

  29. Chung, W.T., Lee, S.H., Kim, J.D., Sung, N.S., Hwang, B., Lee, S.Y., et al., Cytotechnology, 2001, vol. 37, no. 1, pp. 55–64.

    Article  PubMed  CAS  Google Scholar 

  30. Maatooq, G.T., Marzouk, A.M., Gray, A.I., and Rosazza, J.P., Phytochemistry, 2010, vol. 71, nos. 2–3, pp. 262–270.

    Article  PubMed  CAS  Google Scholar 

  31. Chen, J.W., Zhu, Z.Q., Hu, T.X., and Zhu, D.Y., Acta Pharmacol. Sin., 2002, vol. 23, no. 7, pp. 667–672.

    PubMed  CAS  Google Scholar 

  32. Kostrzewa-Susłow, E., Dmochowska-Gładysz, J., and Oszmiański, J., J. Mol. Catal. B: Enzym., 2007, vol. 49, pp. 113–117.

    Article  Google Scholar 

  33. Radwan, M.M., Elsohly, M.A., Slade, D., Ahmed, S.A., Wilson, L., El-Alfy, A.T., et al., Phytochemistry, 2008, vol. 69, no. 14, pp. 2627–2633.

    Article  PubMed  CAS  Google Scholar 

  34. Ibraham, K.A., Radwan, M.M., Ahmed, S.A., Slade, D., Ross, S.A., Elsohly, M.A., and Khan, I.A., Phytochemistry, 2010, vol. 71, nos. 8–9, pp. 1014–1019.

    Article  Google Scholar 

  35. Choudhary, M.I., Siddiqui, Z.A., Musharraf, S.G., Nawaz, S.A., and Atta-Ur-Rahman, Nat. Prod. Res., 2005, vol. 19, no. 4, pp. 311–317.

    Article  PubMed  CAS  Google Scholar 

  36. Choudhary, M.I., Musharraf, S.G., Siddiqui, Z.A., Khan, N.T., Ali, R.A., and Ur-Rahman, A., Chem. Pharm. Bull., 2005, vol. 53, no. 8, pp. 1011–1013.

    Article  PubMed  CAS  Google Scholar 

  37. Padgett, D.A. and Loria, R.M., J. Immunol., 1994, vol. 153, vol. 4, pp. 1544–1552.

    PubMed  CAS  Google Scholar 

  38. Loria, R.M., Padgett, D.A., and Nuynh, P.N., J. Endocrinol., 1996, vol. 150(suppl.), pp. S209–S220.

    PubMed  CAS  Google Scholar 

  39. Loria, R.M., Psychoneuroendocrinology, 1997, vol. 22(suppl. 1), pp. S103–108.

    Article  PubMed  CAS  Google Scholar 

  40. Li, H.-P., Yu, P., Zhang, H.-J., and Liu, H.-M., Chin. J. Chem., 2008, vol. 26, no. 9, pp. 1666–1668.

    Article  CAS  Google Scholar 

  41. Russell, W.R., Scobbie, L., Chesson, A., Richardson, A.J., Stewart, C.S., Duncan, S.H., et al., Nutr. Cancer, vol. 60, no. 5, pp. 636–642.

  42. Gurram, P. S., Girisham, S., and Reddy, S. M., Iranian J. Biotech., 2009, vol. 7, no. 3, pp. 142–147.

    CAS  Google Scholar 

  43. Shyam Prasad, G., Girisham, S., and Reddy, S. M., J. Microbiol. Biotechnol., 2009, vol. 19, no. 9, pp. 922–931

    Article  CAS  Google Scholar 

  44. Srisailam, K. and Veeresham, C., Appl. Biochem. Biotechnol., 2010, vol. 160, no. 7, pp. 2075–2089.

    Article  PubMed  CAS  Google Scholar 

  45. Ma, B., Huang, H.H., Chen, X.Y., Sun, Y.M., Lin, L.H., and Zhong, D.F., Acta Pharmacol. Sin., 2007, vol. 28, no. 7, pp. 1067–1074.

    Article  PubMed  CAS  Google Scholar 

  46. Schmitz, G., Franke, D., Stevens, S., Takors, R., Weuster-Botz, D., and Wandrey, C., J. Mol. Catal. B: Enzym., 2000, vol. 10, no. 1–3, pp. 313–324.

    Article  CAS  Google Scholar 

  47. Mazier. C., Jaouen. M., Sari, M.A., and Buisson, D., Bioorg. Med. Chem. Lett., 2004, vol. 14, no. 21, pp. 5423–5426.

    Article  PubMed  CAS  Google Scholar 

  48. Parshikov, I.A., Freeman, J.P., O. Lay, J., Jr., Beger, R.D., Williams, A.J., and Sutherland, J.B., FEMS Microbiol. Lett., 1999, vol. 177, no. 1, pp. 131–135.

    Article  PubMed  CAS  Google Scholar 

  49. Prasad, G. S., Girisham, S., and Reddy, S.M., Indian J. Exp. Biol., 2010, vol. 48, no. 4, pp. 415–420.

    CAS  Google Scholar 

  50. Verma, A.K., Khemaria, P. Gupta, J., Singh, D.P., Joshi, B.S., Roy, R., et al., Arkivoc., 2010, vol. 9, pp. 1–11.

    Article  Google Scholar 

  51. Li, W., Josephs, J.L., Skiles, G.L., and Humphreys, W.G., Drug. Metab. Dispos., 2008, vol. 36, no. 4, pp. 721–730.

    Article  PubMed  CAS  Google Scholar 

  52. Das, J., Chen, P., Norris, D., Padmanabha, R., Lin, J., Moquin, R.V., et al., J. Med. Chem., 2006, vol. 49, no. 23, pp. 6819–6826.

    Article  PubMed  CAS  Google Scholar 

  53. Potin, D., Monatlik, F., Malabre, P., Fabreguettes, M., Fouquet, A., et al., J. Med. Chem., 2006, vol. 49, no. 24, pp. 6946–6949.

    Article  PubMed  CAS  Google Scholar 

  54. Puzantian, T., Am. J. Health Syst. Pharm., 1998, vol. 55, no. 1, pp. 44–49.

    PubMed  CAS  Google Scholar 

  55. Stimmel, G.L., Dopheide, J.A., and Stahl, S.M., Pharmacotherapy, 1997, vol. 17, no. 1, pp. 10–21.

    PubMed  CAS  Google Scholar 

  56. Martinez, F., del Campo, C., Sinisterra, J.V, and Llama, E.F., Tetrahedron: Asymmetry, 2000, vol. 11, no. 23, pp. 4651–4660.

    Article  CAS  Google Scholar 

  57. Martinez, F., del Campo, C., Sinisterra, J.V, and Llama, E.F., Enzyme Microb. Technol., 2002, vol. 30, no. 3, pp.895–901.

    Google Scholar 

  58. Macías, F.A., Molinillo, J.M., Galindo, J.C., Varela, R.M., Simonet, A.M., and Castellano, D.J., Crop. Prod., 2001, vol. 4, no. 2, pp. 237–255.

    Article  Google Scholar 

  59. Macías, F.A., Marín, D., Oliveros-Bastidas, A., Chinchilla, D., Simonet, A.M., and Molinillo, J.M.G., J. Agric. Food Chem., 2006, vol. 54, no. 4, pp. 991–1000.

    Article  PubMed  Google Scholar 

  60. Vallea, A., Cabreraa, G., Molinillob, J.M.G., Gómeza, J.M., Macías, F.A., and Cantero, D., Process Biochem., 2011, vol. 46, no. 1, pp. 358–364.

    Article  Google Scholar 

  61. Esteve-Núñez, A., Caballero, A., and Ramos, J.L., Microbiol. Mol. Biol. Rev., 2001, vol. 65, no. 3, pp. 335–352.

    Article  PubMed  Google Scholar 

  62. Yang, S.L., Lan, J., and Xu, J.T., Chin. Tradit. Herb. Drugs, 2000, vol. 3l, no. 1, pp. 66–69.

    Google Scholar 

  63. Ojemann, L.M., Nelson, W.L., Shin, D.S., Rowe, A.O., and Buchanan, R.A., Epilepsy Behav., 2006, vol. 8, no. 2, pp. 376–383.

    Article  PubMed  Google Scholar 

  64. Jin, W.S. and Tian, D.Q., Chin. Tradit. Drugs Technol., 2000, vol. 2, pp. 21–23.

    Google Scholar 

  65. Gong, X.D. and Sucher, N.J., Trends Pharm., 1999, vol. 20, no. 5, pp. 191–196.

    Article  CAS  Google Scholar 

  66. Wang, X. and Zhou, M.M., West China J. Pharm. Sci., 2003, vol. 18, pp. 269–270.

    CAS  Google Scholar 

  67. Zhang, H.F., He, G.Q., Liu, J., Ruan, H., Chen Q.H., Zhang, Q., et al., Enzyme Microb. Technol., 2008, vol. 43, pp. 25–30.

    Article  CAS  Google Scholar 

  68. Abel, A.M., Carnell, A. J., Davis, J.A., and Paylor, M., Biotechnol. Lett., 2002, vol. 24, no. 15, pp. 1291–1294.

    Article  CAS  Google Scholar 

  69. Abel, A.M., Carnell, A. J., Davis, J.A., and Paylor, M., Enzyme. Microb. Technol., 2003, vol. 33, no. 5, pp. 743–748.

    Article  CAS  Google Scholar 

  70. Clader, J.W., Curr. Top. Med. Chem., 2005, vol. 5, no. 3, pp. 243–56.

    Article  PubMed  CAS  Google Scholar 

  71. May, S.W., Curr. Opin. Biotechnol., 1999, vol. 10, no. 4, pp. 370–375.

    Article  PubMed  CAS  Google Scholar 

  72. Patel, R.N., Coord. Chem. Rev., 2008, vol. 252, no. 5, pp. 659–701.

    Article  CAS  Google Scholar 

  73. Singh, A., Basit, A., and Banerjee, U.C., J. Ind. Microbiol. Biotechnol., 2009, vol. 36, no. 11, pp. 1369–1374.

    Article  PubMed  CAS  Google Scholar 

  74. Kyslíkováa, E., Babiak, P., Mareováa, H., Palyzováa, A., Hájíek, J., and Kyslíka, P., J. Mol. Catal. B: Enzym., 2010, vol. 67, nos. 3–4, pp. 266–270.

    Article  Google Scholar 

  75. Hamon, D.P., Massy-Westropp, R.A., and Newton, J.L., Tetrahedron, 1995, vol. 51, no. 46, pp. 12645–12660.

    Article  CAS  Google Scholar 

  76. Federsel, H-J., Chemtech., 1993, vol. 23, no. 12, pp. 24–33.

    CAS  Google Scholar 

  77. US Patent No. 002505, 1994.

  78. Gong, P.F., Wu, H.Y., Xu, J.H., Shen, D., and Liu, Y.Y., Appl. Microbiol. Biotechnol., 2002, vol. 58, no. 6, pp. 728–734.

    Article  PubMed  CAS  Google Scholar 

  79. Liu, J., Zhang, Y., Qiu. Lh., Yang, F., Ye, L., and Xia, Y.J., Ind. Microbiol. Biotechnol., 2004, vol. 31, no. 11, pp. 495–499.

    Article  CAS  Google Scholar 

  80. Carvalho, P.O., Calafatti, S.A., Marassi, M., Silva, D.M., Contesini, F.J., Bizaco, R., and Macedo, G.A., Quim Nova, 2005, vol. 28, no. 4, pp. 614–621.

    Article  CAS  Google Scholar 

  81. Carvalho, P.O., Contesini, F.J., Almeida, A.P., and Macedo, G.A., Food Biotechnol., 2005, vol. 19, no. 3, pp. 183–192.

    Article  CAS  Google Scholar 

  82. Carvalho, P.O., Contesini, F.J., Bizaco, R., Calafatti, S.A., and Macedo, G.A., J. Ind. Microbiol. Biotechnol., 2006, vol. 33, no. 8, pp. 713–718.

    Article  CAS  Google Scholar 

  83. Damle, S.V., Patil, P.N., and Salunkhe, M.M., Bioorg. Med. Chem., 2000, vol. 8, no. 8, pp. 2067–2070.

    Article  PubMed  CAS  Google Scholar 

  84. Schulz, B. and Boyle, C., Mycol. Res., 2005, vol. 109, no. 6, pp. 661–686.

    Article  PubMed  Google Scholar 

  85. Borges, K.B., Bonato, P.S., and Pupo, M.T., Quim. Nova, 2011, vol. 34, no. 8, pp. 1354–1357.

    Article  CAS  Google Scholar 

  86. Borges, K.B., Borges, W.S., Pupo, M.T., and Bonato, P.S., Appl. Microbiol. Biotechnol., 2007, vol. 77, no. 3, pp. 669–674.

    Article  PubMed  CAS  Google Scholar 

  87. US Patent No. 0055063 A1, 2003.

  88. US Patent No. 0022899 A1, 2003.

  89. Hanson, R.L., Parker, W.L., Brzozowski, D.B., Tully, T.P., Liu, M., Kotnis A., and Patel, R.N., Tetrahedron: Asymmetry, 2005, vol. 16, no. 16, pp. 2711–2716.

    Article  CAS  Google Scholar 

  90. Dorazil-Dudzik, M., Mika, J., Schafer, M.K., Li, Y., Obara, I., Wordliczek, J., and Przewocka, B., Anesth Analg., 2004, vol. 98, no. 6, pp. 1566–1573.

    Article  PubMed  CAS  Google Scholar 

  91. Sweitzer, S.M., Schubert, P., and DeLeo, J.A., J. Pharmacol. Exp. Ther., 2001, vol. 297, no. 3, pp. 1210–1217.

    PubMed  CAS  Google Scholar 

  92. Wong, J.S, Keyes, S.R, Herbst, R., Coleman, C.N., and Teicher, B.A., Oncol. Res., vol. 8, pp. 513–518.

  93. Margolin, K., Atkins, M., Sparano, J., Sosman, J., Weiss, G., Lotze, M., et al., Clin. Cancer. Res., vol. 3, no. 4, pp. 565–572.

  94. List, A.F., Maziarz, R., Stiff, P., Jansen, J., Liesveld, J., Andrews, F., et al., Bone Marrow Transplant., 2000, vol. 25, no. 3, pp. 283–291.

    Article  PubMed  CAS  Google Scholar 

  95. US Patent No. 5407815, 1995.

  96. Pekala, E., Kochan, M., and Carnell, A.J., Lett. Appl. Microbiol., 2009, vol. 48, no. 1, pp. 19–24.

    Article  PubMed  CAS  Google Scholar 

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  1. Faculty of Pharmacy and Alternative Medicine, Islamia University of Bahawalpur, Bahawalpur, 63100, Pakistan

    I. Pervaiz, S. Ahmad, M. A. Madni, H. Ahmad & F. H. Khaliq

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Pervaiz, I., Ahmad, S., Madni, M.A. et al. Microbial biotransformation: a tool for drug designing. Appl Biochem Microbiol 49, 437–450 (2013). https://doi.org/10.1134/S0003683813050098

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