Advertisement

Glutathione Production in Yeast

  • Anand K. Bachhawat
  • Dwaipayan Ganguli
  • Jaspreet Kaur
  • Neha Kasturia
  • Anil Thakur
  • Hardeep Kaur
  • Akhilesh Kumar
  • Amit Yadav

Glutathione, γ -glutamyl-cysteinyl-glycine, is the most abundant non-protein thiol found in almost all eukaryotic cells (and in some prokaryotes). The tripeptide, which is synthesized non-ribosomally by the consecutive action of two soluble enzymes, is needed for carrying out numerous functions in the cell, most important of which is the maintenance of the redox buffer. The cycle of glutathione biosynthesis and degradation forms part of the γ -glutamyl cycle in most organisms although the latter half of the pathway has not been demonstrated in yeasts. Our current understanding of how glutathione levels are controlled at different levels in the cell is described. Several different routes and processes have been attempted to increase commercial production of glutathione using both yeast and bacteria. In this article we discuss the history of glutathione production in yeast. The current bottlenecks for increased glutathione production are presented based on our current understanding of the regulation of glutathione homeostasis, and possible strategies for overcoming these limitations for further enhancing and improving glutathione production are discussed

Keywords

Glutathione sulphur yeast biosynthesis rate-limiting steps 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Alfafara, C.G., Kanda, A., Shioi, T., Shimizu, H., Shioya, S., and Suga, K. 1992. Appl. Microbiol. Biotechnol. 36: 538–540.CrossRefGoogle Scholar
  2. Alfafara, C.G., Miura, K., Shimizu, H., Shioya, S., Suga, K., and Suzuki, K. 1993. Biotechnol. Bioeng. 41: 493–501.CrossRefGoogle Scholar
  3. Amssoms, K., Oza, S.L., Augustyns, K., Yamani, A., Lambeir, A.M., Bal, G., Veken, P.V., Fairlamb, A.H., and Haemers, A. 2002a. Bioorg. Med. Chem. Lett. 12: 2703–2705.CrossRefGoogle Scholar
  4. Amssoms, K., Oza, S.L., Ravaschino, E., Yamani, A., Lambeir, A.M., Rajan, P., Bal, G., Rodriguez, J.B., Fairlamb, A.H., Augustyns, K., and Haemers, A. 2002b. Bioorg. Med. Chem. Lett. 12: 2553–2556.CrossRefGoogle Scholar
  5. Bloch, K. 1949. J Biol Chem. 179: 1245–1254.Google Scholar
  6. Bourbouloux, A., Shahi, P., Chakladar, A., Delrot, S., and Bachhawat, A.K. 2000. J. Biol. Chem. 275: 13259–65.CrossRefGoogle Scholar
  7. Brombacher, K., Fischer, B.B., Rufenacht, K., and Eggen, R.I.L. 2006. Yeast 23: 741–750.CrossRefGoogle Scholar
  8. Brzywczy, J., Sienko, M., Kucharska, A., and Paszewski, A. 2002. Yeast 19: 29–35.CrossRefGoogle Scholar
  9. Castro, V.M., Kelley, M.K., Engqvist-Goldstein, A., and Kauvar, L.M. 1993. Biochem. J. 292: 371–377.Google Scholar
  10. Cha, J.Y., Park, J.C., Jeon, B.S., Lee, Y.C., and Cho, Y.S. 2004. J. Microbiol. 42: 51–55.Google Scholar
  11. Chaudhuri. B., Ingavale, S., and Bachhawat, A.K. 1997. Genetics 145: 75–83.Google Scholar
  12. Chen, Y., Shertzer, H.G., Schneider, S.N., Nebert, D.W., and Dalton, T.P. 2005. J. Biol. Chem. 280: 33766–33774.CrossRefGoogle Scholar
  13. Cooke, R.W. and Drury, J.A. 2005. Biol. Neonate. 87: 178–80.CrossRefGoogle Scholar
  14. Dalton, T.P., Dieter, M.Z., Yang, Y., Shertzer, H.G., and Nebert, D.W. 2000. Biochem. Biophys. Res. Commun. 279: 324–329.CrossRefGoogle Scholar
  15. Daunes, S. and D' silva, C. 2002. Antimicrob. Agents. Chemother. 46: 434–437.CrossRefGoogle Scholar
  16. Dormer, U.H., Westwater, J., McLaren, N.F., Kent, N.A., Mellor, J., and Jamieson, D.J. 2000. J. Biol. Chem. 275: 32611–32616.CrossRefGoogle Scholar
  17. Dormer, U.H., Westwater, J., Stephen, D.W.S., and Jamieson, D.J. 2002. Biochem. Biophy. Acta. 1576: 23–29.Google Scholar
  18. During-Olsen, L., Regenberg, B., Gjermansen, C., Kielland-Brandt, M.C., and Hansen, J. 1999. Curr. Genet. 35: 609–617.CrossRefGoogle Scholar
  19. Fahey, R.C. and Sundquist, A.R. 1991. Adv. Enzymol. RAMolB. 64: 1–44.CrossRefGoogle Scholar
  20. Fauchon, M., Lagniel, G., Aude, J.C., Lombardia, L., Soularue, P., Petat, C., Marguerie, G., Sentenac, A., Werner, M., and Labarre, J. 2002. Mol. Cell. 9: 713–23.CrossRefGoogle Scholar
  21. Ganguli, D., Kumar, C., and Bachhawat, A.K. 2007. Genetics 175: 117–1151.Google Scholar
  22. Ganguly, D., Srikanth, C.V., Kumar, C., Vats, P., and Bachhawat, A.K. 2003. IUBMB Life 55: 553–554.CrossRefGoogle Scholar
  23. Grant, C.M., MacIver, F.H., and Dawes, I.W. 1996. Curr Genet. 29: 511–5.CrossRefGoogle Scholar
  24. Grant, C.M., MacIver, F.H., and Dawes, I.W. 1997. Mol. Biol. Cell. 8: 1699–1707.Google Scholar
  25. Gushima, H., Miya, T., Murata, k., and Kimura, A. 1983. J. Appl. Biochem. 5: 43–52.Google Scholar
  26. Harington, C.R. and Mead, T.H. 1935. Biochem. J. 29: 1602–1611.Google Scholar
  27. Hopkins, F.G. 1921. Biochem. J. 15: 286.Google Scholar
  28. Hopkins, F.G. 1929. J. Biol. Chem. 84: 269.Google Scholar
  29. Hunter, G. and Eagles, B.A. 1927. J. Biol. Chem. 72: 703.Google Scholar
  30. Ishii, S. and Miyajima, R. 1989. JP Patent 1, 141,591.Google Scholar
  31. Kaur, J. and Bachhawat, A.K. 2007. Genetics (In Press).Google Scholar
  32. Kazuhiro, H., Junichi, I., Shogo, F., Masahiro, N. 2003 (JP200428312).Google Scholar
  33. Kazuhiro, H., Masahiro, N., Zaido, M.S., Susumu, K., Shogo, F., Osamu, M., and Junichi, I. 2002. (JP2003284547A).Google Scholar
  34. Kimura, A., and Murata, K. 1986 USP 4,598, 046.Google Scholar
  35. Kumar, C., Sharma, R., and Bachhawat, A. K. 2003a. FEMS Microbiol Lett. 219: 187–194.CrossRefGoogle Scholar
  36. Kumar, C., Sharma, R., and Bachhawat, A.K. 2003b. Yeast 20: 857–63.CrossRefGoogle Scholar
  37. Lafaye, A., Junot, C., Pereira, Y., Lagniel, G., Tabet, J.C., Ezan, E., and Labarre, J. 2005. J Biol Chem. 280: 24723–24730.CrossRefGoogle Scholar
  38. Lang-Hinrichs, C., and Stahl, U. 1988. EP0300168A2.Google Scholar
  39. Li, Y., Chen, J., Zhou, N., Fu, W., Ruan, W., and Lun, S. 1998. Chin. J. Biotechnol. 14: 85–91.Google Scholar
  40. Li, Y., Hugenholtz, j., Abee, T., and Molenaar, D. 2003. Appl. Environ. Microbiol. 69: 5739–5745.CrossRefGoogle Scholar
  41. Li, Y., Hugenholtz, J., Sybesma, W., Abee, T., and Molenaar, D. 2005. Appl. Microbiol. Biotechnol. l67: 83–90.CrossRefGoogle Scholar
  42. Li, Y., Wei, G., and Chen, J. 2004. Appl. Microbiol. Biotechnol. 66: 233–242.CrossRefGoogle Scholar
  43. Liao, X.Y., Shen, W., Chen, J., Li, Y., and Du, G.C. 2006. Lett. Appl. Microbiol. 43: 211–214.CrossRefGoogle Scholar
  44. Lin. J.-P., Tian, J., You, J.-F., Jin, Z.-H., Xu, Z.-N., and Cen, P.-L. 2004. Biochem. Eng. J. 21: 19–25.CrossRefGoogle Scholar
  45. Liu, Y., Hama, H., Fujita, Y., Kondo, A., Inoue, Y., Kimura, A., and Fukuda, H. 1999b. Biotechnol. Bioeng. 64: 54–60.CrossRefGoogle Scholar
  46. Liu, C.H., Hwang, C.-F., and Liao, C.-C. 1999a. Process Biochem. 34: 17–23.CrossRefGoogle Scholar
  47. Liu, H., Lin, J.P., Cen, P.L., and Pan, Y.J. 2004. Process Biochem. 39: 1993–1997.CrossRefGoogle Scholar
  48. Lueder, D.V., and Phillips, M.A. 1996. J. Biol. Chem. 271: 17485–17490.CrossRefGoogle Scholar
  49. Meister, A. 1988. Trends Biochem. Sci. 13: 185–188.CrossRefGoogle Scholar
  50. Meister, A., and Anderson, M.E. 1983. Annu. Rev. Biochem. 52: 711–760.CrossRefGoogle Scholar
  51. Miwa, N. 1976. Glutathione. JP patent 51, 144, 789.Google Scholar
  52. Nie, W., Wei, G., Du, G., Li, Y., and Chen, J. 2005. Lett. Appl. Microbiol. 40: 378–384.CrossRefGoogle Scholar
  53. Ohtake, Y., Watanabe, K., Tezuka, H., Ogata, T., Yabuuchi, S., Murata, K., and Kimura, A. 1988. Agric. Biol. Chem. 52: 2753–2762.Google Scholar
  54. Ohtake, Y., Watanabe, K., Tezuka, H., Ogata, T., Yabuuchi, S., Murata, K., and Kimura, 1989. J. Ferment. Bioeng. 68: 390–399.CrossRefGoogle Scholar
  55. Orlowski, M., and Meister, A. 1970. Proc Natl Acad Sci USA. 67: 1248–55.CrossRefGoogle Scholar
  56. Ostergaard, H., Henriksen, A., Hansen, F.G., and Winther, J.R. 2004. J. Cell Biol. 166: 337–345.CrossRefGoogle Scholar
  57. Pailhade, R.J. de. 1888. Bull. Soc. Hist. Nat. Toulouse 173.Google Scholar
  58. Perrone, G.G., Grant, C.M., and Dawes, I.W. 2005. Mol. Biol. Cell 16: 218–230.CrossRefGoogle Scholar
  59. Pirie, N.W., and Pinhey, K.G. 1929. J. Biol. Chem. 84: 657.Google Scholar
  60. Reid, M., and Jahoor, F. 2001. Curr. Opin. Clin. Nutr. Metab. Care. 4: 65–71.CrossRefGoogle Scholar
  61. Richman, P.G., and Meister, A. 1975. J. Biol. Chem. 250: 1422–1426.Google Scholar
  62. Rosen, L.S., Laxa, B., Boulos, L.,Wiggins, L., Keck, J.G., Jameson, A.J., Parra, R., Patel, K., and Brown, G.L. 2004. Clin. Cancer. Res. 10: 3689–3698.CrossRefGoogle Scholar
  63. Sakato, K., and Tanaka, H. 1992. Biotechnol. Bioeng. 40: 904–912.CrossRefGoogle Scholar
  64. Sawa, Y., Shindo, H., Nishimura, S., and Ochiai, H. 1986. Agric. Biol. Chem. 50: 1361–1363.Google Scholar
  65. Schafer, F.Q., and Buettner, G.R. 2001 Free Radical Bio. Med. 30: 1191–1212.CrossRefGoogle Scholar
  66. Schultz, M., Dutta, S., and Tew, K.D. 1997. Adv. Drug Deliv. Rev. 26: 91–104.CrossRefGoogle Scholar
  67. Shimizu, H., Araki, K., and Shioya, S., Suga, K. 1991. Biotechnol. Bioeng. 38: 196–205.CrossRefGoogle Scholar
  68. Sies, H. 1999. Free Radical Bio. Med. 27: 916–921.CrossRefGoogle Scholar
  69. Smirnova, G.V., and Oktyabrsky, N. 2005. Biochemistry (Moscow).: 701199–1211.Google Scholar
  70. Springael, J.Y., and Penninckx, M.J. 2003. Biochem. J. 371: 589–95.CrossRefGoogle Scholar
  71. Srikanth, C.V., Vats, P., Bourbouloux, A., Delrot, S., and Bachhawat, A.K. 2005. Curr Genet. 47: 345–358.CrossRefGoogle Scholar
  72. Stephen, D.W., and Jamieson, D.J. 1997. Mol. Microbiol. 23: 203–210.CrossRefGoogle Scholar
  73. Stipanuk, M.H., Dominy, J.E Jr., Lee, J.-I. and Coloso, R.M. 2006. 5th Amino acid Assessment Workshop.Google Scholar
  74. Sugiyama, K., Izawa, S., and Inoue, Y. 2000. J. Biol. Chem. 275: 15535–15540.CrossRefGoogle Scholar
  75. Thomas, D., Jacquemin, I., and Surdin-Kerjan, Y. 1992. Mol. Cell.Biol. 12: 1719–1727.Google Scholar
  76. Thomas, D., and Surdin-Kerjan, Y. 1997. Microbiol. Mol. Biol. Rev. 61: 503–532.Google Scholar
  77. Udeh, K.O., and Achremowicz, B. 1997. Acta. Microbiol. Pol. 46: 105–114.Google Scholar
  78. Wei, G., Li, Y., and Du, G., Chen J. 2003. Biotechnol. Lett. 25: 887–890.CrossRefGoogle Scholar
  79. Wen, S., Zhang, T., and Tan T. 2004. Enzyme Microbial. Tech. 35: 501–507.CrossRefGoogle Scholar
  80. Wen, S., Zhang, T., and Tan, T. 2005. Process Biochem. 42: 3474–3479.CrossRefGoogle Scholar
  81. Wen, S., Zhang, T., and Tan, T. 2006. Process Biochem. (In Press)Google Scholar
  82. Wheeler, G.L., Quinn, K.A., Perrone, G., Dawes, I.W. and Grant, C.M. 2002. Mol. Microbiol. 46: 545–556.CrossRefGoogle Scholar
  83. Wheeler, G.L., Quinn, K.A., Perrone, G., Dawes, I.W., and Grant, C.M. 2003. J. Biol. Chem. 278: 49920–49928.CrossRefGoogle Scholar
  84. Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R. and Turner, N.D. 2004. J. Nutr. 134: 489–92.Google Scholar
  85. Youssefian, S., Nakamura, M., Orudgev, E. and Kondo, N. 2001. Plant Physiol. 126: 1001–1011.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media B.V 2009

Authors and Affiliations

  • Anand K. Bachhawat
    • 1
  • Dwaipayan Ganguli
    • 1
  • Jaspreet Kaur
    • 1
  • Neha Kasturia
    • 1
  • Anil Thakur
    • 1
  • Hardeep Kaur
    • 1
  • Akhilesh Kumar
    • 1
  • Amit Yadav
    • 1
  1. 1.Institute of Microbial TechnologyChandigarhIndia

Personalised recommendations