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
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References
Alfafara, C.G., Kanda, A., Shioi, T., Shimizu, H., Shioya, S., and Suga, K. 1992. Appl. Microbiol. Biotechnol. 36: 538–540.
Alfafara, C.G., Miura, K., Shimizu, H., Shioya, S., Suga, K., and Suzuki, K. 1993. Biotechnol. Bioeng. 41: 493–501.
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.
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.
Bloch, K. 1949. J Biol Chem. 179: 1245–1254.
Bourbouloux, A., Shahi, P., Chakladar, A., Delrot, S., and Bachhawat, A.K. 2000. J. Biol. Chem. 275: 13259–65.
Brombacher, K., Fischer, B.B., Rufenacht, K., and Eggen, R.I.L. 2006. Yeast 23: 741–750.
Brzywczy, J., Sienko, M., Kucharska, A., and Paszewski, A. 2002. Yeast 19: 29–35.
Castro, V.M., Kelley, M.K., Engqvist-Goldstein, A., and Kauvar, L.M. 1993. Biochem. J. 292: 371–377.
Cha, J.Y., Park, J.C., Jeon, B.S., Lee, Y.C., and Cho, Y.S. 2004. J. Microbiol. 42: 51–55.
Chaudhuri. B., Ingavale, S., and Bachhawat, A.K. 1997. Genetics 145: 75–83.
Chen, Y., Shertzer, H.G., Schneider, S.N., Nebert, D.W., and Dalton, T.P. 2005. J. Biol. Chem. 280: 33766–33774.
Cooke, R.W. and Drury, J.A. 2005. Biol. Neonate. 87: 178–80.
Dalton, T.P., Dieter, M.Z., Yang, Y., Shertzer, H.G., and Nebert, D.W. 2000. Biochem. Biophys. Res. Commun. 279: 324–329.
Daunes, S. and D' silva, C. 2002. Antimicrob. Agents. Chemother. 46: 434–437.
Dormer, U.H., Westwater, J., McLaren, N.F., Kent, N.A., Mellor, J., and Jamieson, D.J. 2000. J. Biol. Chem. 275: 32611–32616.
Dormer, U.H., Westwater, J., Stephen, D.W.S., and Jamieson, D.J. 2002. Biochem. Biophy. Acta. 1576: 23–29.
During-Olsen, L., Regenberg, B., Gjermansen, C., Kielland-Brandt, M.C., and Hansen, J. 1999. Curr. Genet. 35: 609–617.
Fahey, R.C. and Sundquist, A.R. 1991. Adv. Enzymol. RAMolB. 64: 1–44.
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.
Ganguli, D., Kumar, C., and Bachhawat, A.K. 2007. Genetics 175: 117–1151.
Ganguly, D., Srikanth, C.V., Kumar, C., Vats, P., and Bachhawat, A.K. 2003. IUBMB Life 55: 553–554.
Grant, C.M., MacIver, F.H., and Dawes, I.W. 1996. Curr Genet. 29: 511–5.
Grant, C.M., MacIver, F.H., and Dawes, I.W. 1997. Mol. Biol. Cell. 8: 1699–1707.
Gushima, H., Miya, T., Murata, k., and Kimura, A. 1983. J. Appl. Biochem. 5: 43–52.
Harington, C.R. and Mead, T.H. 1935. Biochem. J. 29: 1602–1611.
Hopkins, F.G. 1921. Biochem. J. 15: 286.
Hopkins, F.G. 1929. J. Biol. Chem. 84: 269.
Hunter, G. and Eagles, B.A. 1927. J. Biol. Chem. 72: 703.
Ishii, S. and Miyajima, R. 1989. JP Patent 1, 141,591.
Kaur, J. and Bachhawat, A.K. 2007. Genetics (In Press).
Kazuhiro, H., Junichi, I., Shogo, F., Masahiro, N. 2003 (JP200428312).
Kazuhiro, H., Masahiro, N., Zaido, M.S., Susumu, K., Shogo, F., Osamu, M., and Junichi, I. 2002. (JP2003284547A).
Kimura, A., and Murata, K. 1986 USP 4,598, 046.
Kumar, C., Sharma, R., and Bachhawat, A. K. 2003a. FEMS Microbiol Lett. 219: 187–194.
Kumar, C., Sharma, R., and Bachhawat, A.K. 2003b. Yeast 20: 857–63.
Lafaye, A., Junot, C., Pereira, Y., Lagniel, G., Tabet, J.C., Ezan, E., and Labarre, J. 2005. J Biol Chem. 280: 24723–24730.
Lang-Hinrichs, C., and Stahl, U. 1988. EP0300168A2.
Li, Y., Chen, J., Zhou, N., Fu, W., Ruan, W., and Lun, S. 1998. Chin. J. Biotechnol. 14: 85–91.
Li, Y., Hugenholtz, j., Abee, T., and Molenaar, D. 2003. Appl. Environ. Microbiol. 69: 5739–5745.
Li, Y., Hugenholtz, J., Sybesma, W., Abee, T., and Molenaar, D. 2005. Appl. Microbiol. Biotechnol. l67: 83–90.
Li, Y., Wei, G., and Chen, J. 2004. Appl. Microbiol. Biotechnol. 66: 233–242.
Liao, X.Y., Shen, W., Chen, J., Li, Y., and Du, G.C. 2006. Lett. Appl. Microbiol. 43: 211–214.
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.
Liu, Y., Hama, H., Fujita, Y., Kondo, A., Inoue, Y., Kimura, A., and Fukuda, H. 1999b. Biotechnol. Bioeng. 64: 54–60.
Liu, C.H., Hwang, C.-F., and Liao, C.-C. 1999a. Process Biochem. 34: 17–23.
Liu, H., Lin, J.P., Cen, P.L., and Pan, Y.J. 2004. Process Biochem. 39: 1993–1997.
Lueder, D.V., and Phillips, M.A. 1996. J. Biol. Chem. 271: 17485–17490.
Meister, A. 1988. Trends Biochem. Sci. 13: 185–188.
Meister, A., and Anderson, M.E. 1983. Annu. Rev. Biochem. 52: 711–760.
Miwa, N. 1976. Glutathione. JP patent 51, 144, 789.
Nie, W., Wei, G., Du, G., Li, Y., and Chen, J. 2005. Lett. Appl. Microbiol. 40: 378–384.
Ohtake, Y., Watanabe, K., Tezuka, H., Ogata, T., Yabuuchi, S., Murata, K., and Kimura, A. 1988. Agric. Biol. Chem. 52: 2753–2762.
Ohtake, Y., Watanabe, K., Tezuka, H., Ogata, T., Yabuuchi, S., Murata, K., and Kimura, 1989. J. Ferment. Bioeng. 68: 390–399.
Orlowski, M., and Meister, A. 1970. Proc Natl Acad Sci USA. 67: 1248–55.
Ostergaard, H., Henriksen, A., Hansen, F.G., and Winther, J.R. 2004. J. Cell Biol. 166: 337–345.
Pailhade, R.J. de. 1888. Bull. Soc. Hist. Nat. Toulouse 173.
Perrone, G.G., Grant, C.M., and Dawes, I.W. 2005. Mol. Biol. Cell 16: 218–230.
Pirie, N.W., and Pinhey, K.G. 1929. J. Biol. Chem. 84: 657.
Reid, M., and Jahoor, F. 2001. Curr. Opin. Clin. Nutr. Metab. Care. 4: 65–71.
Richman, P.G., and Meister, A. 1975. J. Biol. Chem. 250: 1422–1426.
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.
Sakato, K., and Tanaka, H. 1992. Biotechnol. Bioeng. 40: 904–912.
Sawa, Y., Shindo, H., Nishimura, S., and Ochiai, H. 1986. Agric. Biol. Chem. 50: 1361–1363.
Schafer, F.Q., and Buettner, G.R. 2001 Free Radical Bio. Med. 30: 1191–1212.
Schultz, M., Dutta, S., and Tew, K.D. 1997. Adv. Drug Deliv. Rev. 26: 91–104.
Shimizu, H., Araki, K., and Shioya, S., Suga, K. 1991. Biotechnol. Bioeng. 38: 196–205.
Sies, H. 1999. Free Radical Bio. Med. 27: 916–921.
Smirnova, G.V., and Oktyabrsky, N. 2005. Biochemistry (Moscow).: 701199–1211.
Springael, J.Y., and Penninckx, M.J. 2003. Biochem. J. 371: 589–95.
Srikanth, C.V., Vats, P., Bourbouloux, A., Delrot, S., and Bachhawat, A.K. 2005. Curr Genet. 47: 345–358.
Stephen, D.W., and Jamieson, D.J. 1997. Mol. Microbiol. 23: 203–210.
Stipanuk, M.H., Dominy, J.E Jr., Lee, J.-I. and Coloso, R.M. 2006. 5th Amino acid Assessment Workshop.
Sugiyama, K., Izawa, S., and Inoue, Y. 2000. J. Biol. Chem. 275: 15535–15540.
Thomas, D., Jacquemin, I., and Surdin-Kerjan, Y. 1992. Mol. Cell.Biol. 12: 1719–1727.
Thomas, D., and Surdin-Kerjan, Y. 1997. Microbiol. Mol. Biol. Rev. 61: 503–532.
Udeh, K.O., and Achremowicz, B. 1997. Acta. Microbiol. Pol. 46: 105–114.
Wei, G., Li, Y., and Du, G., Chen J. 2003. Biotechnol. Lett. 25: 887–890.
Wen, S., Zhang, T., and Tan T. 2004. Enzyme Microbial. Tech. 35: 501–507.
Wen, S., Zhang, T., and Tan, T. 2005. Process Biochem. 42: 3474–3479.
Wen, S., Zhang, T., and Tan, T. 2006. Process Biochem. (In Press)
Wheeler, G.L., Quinn, K.A., Perrone, G., Dawes, I.W. and Grant, C.M. 2002. Mol. Microbiol. 46: 545–556.
Wheeler, G.L., Quinn, K.A., Perrone, G., Dawes, I.W., and Grant, C.M. 2003. J. Biol. Chem. 278: 49920–49928.
Wu, G., Fang, Y.Z., Yang, S., Lupton, J.R. and Turner, N.D. 2004. J. Nutr. 134: 489–92.
Youssefian, S., Nakamura, M., Orudgev, E. and Kondo, N. 2001. Plant Physiol. 126: 1001–1011.
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Bachhawat, A.K. et al. (2009). Glutathione Production in Yeast. In: Satyanarayana, T., Kunze, G. (eds) Yeast Biotechnology: Diversity and Applications. Springer, Dordrecht. https://doi.org/10.1007/978-1-4020-8292-4_13
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