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Microbial production of glutathione

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Abstract

Glutathione (GSH) is a non-coding tripeptide thiol with several important regulative and protective functions in eukaryotes and in most prokaryotes. The primary function of GSH is to maintain the redox potential of the cell, which is directly connected to GSH concentration, and to prevent cellular damages caused by reactive oxygen species or toxic heavy metals. Due to its antioxidant character, it is widely used in pharmaceutical, cosmetic and food industry. There have been different strategies to optimize GSH yield and productivity in bacteria and yeasts by means of metabolic and evolutionary engineering, media optimization and bioprocess engineering. The fed-batch procedure with yeasts of the genera Saccharomyces and Candida is still common method for industrial production. However, for an economic bioprocess production of GSH key factors like media costs, strain performance and process scalability are essential. Beside the extraction and purification of GSH as bulk product, GSH-enriched yeast cells are used for food and beverage applications, as well. This review outlines current applications of microbially produced GSH and illustrates current developments and strategies for its production.

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References

  • Alfafara CG, Kanda A, Shioi T, Shimizu H, Shioya S, Suga K (1992a) Effect of amino acids on glutathione production by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 36:538–540

    Article  CAS  Google Scholar 

  • Alfafara CG, Miura K, Shimizu H, Shioya S, Suga K (1992b) Cysteine addition strategy for maximum glutathione production in fed-batch culture of Saccharomyces cerevisiae. Appl Microbiol Biotechnol 37:141–146. doi:10.1007/BF00178160

    Article  CAS  Google Scholar 

  • Anderson ME (1998) Glutathione: an overview of biosynthesis and modulation. Chem Biol Interact 111–112:1–14. doi:10.1016/S0009-2797(97)00146-4

    Article  Google Scholar 

  • Anschau A, dos Santos LO, Alegre RM (2013) A cost effective fermentative production of glutathione by Saccharomyces cerevisiae with cane molasses and glycerol. Braz Arch Biol Technol 56:849–857. doi:10.1590/S1516-89132013000500017

    Article  CAS  Google Scholar 

  • Ask M, Mapelli V, Höck H, Olsson L, Bettiga M (2013) Engineering glutathione biosynthesis of Saccharomyces cerevisiae increases robustness to inhibitors in pretreated lignocellulosic materials. Microb Cell Fact. doi:10.1186/1475-2859-12-87

    Google Scholar 

  • Ayer A, Gourlay CW, Dawes IW (2013) Cellular redox homeostasis, reactive oxygen species and replicative ageing in Saccharomyces cerevisiae. FEMS Yeast Res 14:60–72. doi:10.1111/1567-1364.12114

    Article  Google Scholar 

  • Bachhawat AK, Ganguli D, Kaur J, Kasturia N, Thakur A, Kaur H, Kumar A, Yadav A (2009) Glutathione Production in Yeast. In: Satyanarayana T, Kunze G (eds) Yeast biotechnology: diversity and applications. Springer Netherlands, Dordrecht, pp 259–280

    Chapter  Google Scholar 

  • Bloch K (1949) The synthesis of glutathione in isolated liver. J Biol Chem 179:1245–1254

    CAS  Google Scholar 

  • Buonocore D, Grosini M, Giardina S, Michelotti A, Carrabetta M, Seneci A, Verri M, Dossena M, Marzatico F (2016) Bioavailability study of an innovative orobuccal formulation of glutathione. Oxid Med Cell. Longev 2016:3286365. doi:10.1155/2016/3286365

    Article  Google Scholar 

  • Cai J, Changgao W (2012) Preparation method of glutathione-enriched yeast. China Patent Application CN102653722 (A)

  • Cha J, Park J, Jeon B, Lee Y, Cho Y (2004) Optimal fermentation conditions for enhanced glutathione production by Saccharomyces cerevisiae FF-8. J Microbiol 42:51–55

    CAS  Google Scholar 

  • Chen Y, Yang X, Zhang S, Wang X, Guo C, Guo X, Xiao D (2012) Development of Saccharomyces cerevisiae producing higher levels of sulfur dioxide and glutathione to improve beer flavor stability. Appl Biochem Biotechnol 166:402–413. doi:10.1007/s12010-011-9436-3

    Article  CAS  Google Scholar 

  • Chen J, Xie L, Cai J, Yang C, Duan X (2013) Enzymatic synthesis of glutathione using engineered Saccharomyces cerevisiae. Biotechnol Lett 35:1259–1264. doi:10.1007/s10529-013-1191-9

    Article  CAS  Google Scholar 

  • Cho YS (2010) A method for mass production of glutathione. Republic of Korea Patent Application KR20100040589 (A)

  • Cho DW, Kim JM, Lee DH, Hurh BS, Kim YH, Kim DE, Oh E, Bae HA, Kim JH, Shin SH, Kang DK (2012) Novel yeast mutant containing increased glutathione content, method for producing the same and use thereof. Republic of Korea Patent KR101150148 (B1)

  • Chu D (2013) Combination containing complex nucleoside, glutathione and yeast extract and application of combination in aspects of alleviating hangover and protecting liver. China Patent Application CN102886042 (A)

  • Crum A (2011) Nutritional or therapeutic compositions and methods to increase bodily glutathione levels. United States Reissued Patent USRE42645 (E)

  • Drakulic T, Temple MD, Guido R, Jarolim S, Breitenbach M, Attfield PV, Dawes IW (2005) Involvement of oxidative stress response genes in redox homeostasis, the level of reactive oxygen species, and ageing in Saccharomyces cerevisiae. FEMS Yeast Res 5:1215–1228. doi:10.1016/j.femsyr.2005.06.001

    Article  CAS  Google Scholar 

  • Elskens MT, Jaspers CJ, Penninckx MJ (1991) Glutathione as an endogenous sulphur source in the yeast Saccharomyces cerevisiae. J Gen Microbiol 137:637–644. doi:10.1099/00221287-137-3-637

    Article  CAS  Google Scholar 

  • Fei L, Wang Y, Chen S (2009) Improved glutathione production by gene expression in Pichia pastoris. Bioprocess Biosyst Eng 32:729–735. doi:10.1007/s00449-009-0297-x

    Article  CAS  Google Scholar 

  • Fu D (2015) Yeast glutathione nutrition preparation. China Patent CN103750344 (B)

  • Fukabori H, Hamada K, Inoue Y, Ito C, Watanabe H, Yasuda N (2012) Method for creating baker’s yeast with enhanced glutathione production. Japan Patent Application JP2012213361 (A)

  • Hara KY, Aoki N, Kobayashi J, Kiriyama K, Nishida K, Araki M, Kondo A (2015) Improvement of oxidized glutathione fermentation by thiol redox metabolism engineering in Saccharomyces cerevisiae. Appl Microbiol Biotechnol 99:9771–9778. doi:10.1007/s00253-015-6847-z

    Article  CAS  Google Scholar 

  • Harington CR, Mead TR (1935) Synthesis of glutathione. Biochem J 29:1602–1611

    Article  CAS  Google Scholar 

  • Hersh T (1999) Intra-oral antioxidant preparations. United States Patent Application US5906811 (A)

  • Hongtao B (2010) Glutathione fermentation production method. China Patent Application CN101824451 (A)

  • Hopkins FG (1929) On glutathione: a reinvestigation. J Biol Chem 84:269–320

    CAS  Google Scholar 

  • Kazuhiko T, Yoshiyuki Y (2014) Method for production of glutathione or gamma-glutamylcysteine. United States Patent US8647839 (B2)

  • Kim YC (2016) Novel yeast overproducing glutathione and method for glutathione overproduction by using it. Republic of Korea Patent KR101612421 (B1)

  • Kiriyama K, Hara KY, Kondo A (2013) Oxidized glutathione fermentation using Saccharomyces cerevisiae engineered for glutathione metabolism. Appl Microbiol Biotechnol 97:7399–7404. doi:10.1007/s00253-013-5074-8

    Article  CAS  Google Scholar 

  • Kurylenko OO, Yurkiv MT, Dmytruk KV, Sybirnyi AA (2016) Method for producing recombinant strains of methylotrophic yeast Hansenula polymorpha capable of glutathione overexpression. Ukraine Patent UA111511 (C2)

  • Lee WS, Kim HS, Lee HJ, Sang KB, Ki KS, Kim SW, Chang CS, Joo HS, Seo YI, Yu JN (2010) The mutant of Saccharomyces cerevisiae producing glutathione to high concentrations and the mass production method of glutathione by culturing the mutant of Saccharomyces cerevisiae. Republic of Korea Patent Application. KR20100095829 (A)

  • Lee HG, Koo SH, Lim DY, Kim ES, Yoon HS, Lee JS, Kim GH (2015) Method for the production of food packaging film with enhanced glutathione stability. Republic of Korea Patent KR101492471 (B1)

  • Li Y, Wei G, Chen J (2004) Glutathione: a review on biotechnological production. Appl Microbiol Biotechnol 66:233–242. doi:10.1007/s00253-004-1751-y

    Article  CAS  Google Scholar 

  • Li W, Li Z, Ye Q (2010) Enzymatic synthesis of glutathione using yeast cells in two-stage reaction. Bioprocess Biosyst Eng 33:675–682. doi:10.1007/s00449-009-0361-6

    Article  CAS  Google Scholar 

  • Li Z, Ye Q, Li W, Zhang S (2014) Method for producing glutathione by fermentation of recombinant Escherichia coli. China Patent CN102586369 (B)

  • Liang G, Du G, Chen J (2008a) A novel strategy of enhanced glutathione production in high cell density cultivation of Candida utilis—Cysteine addition combined with dissolved oxygen controlling. Enzyme Microb Technol 42:284–289. doi:10.1016/j.enzmictec.2007.10.008

    Article  CAS  Google Scholar 

  • Liang G, Du G, Chen J (2008b) Enhanced glutathione production by using low-pH stress coupled with cysteine addition in the treatment of high cell density culture of Candida utilis. Lett Appl Microbiol 46:507–512. doi:10.1111/j.1472-765X.2008.02352.x

    Article  CAS  Google Scholar 

  • Liang G, Liao X, Du G, Chen J (2008c) Elevated glutathione production by adding precursor amino acids coupled with ATP in high cell density cultivation of Candida utilis. J Appl Microbiol 105:1432–1440. doi:10.1111/j.1365-2672.2008.03892.x

    Article  CAS  Google Scholar 

  • Liang G, Liao X, Du G, Chen J (2009) A new strategy to enhance glutathione production by multiple H2O2 induced oxidative stresses in Candida utilis. Bioresour Technol 100:350–355. doi:10.1016/j.biortech.2008.06.012

    Article  CAS  Google Scholar 

  • Liang G, Mo Y, Du G (2010) Optimization of sodium dedecyl sulfate (SDS) addition coupled with adenosine triphosphate (ATP) regeneration for glutathione overproduction in high density cultivation of Candida utilis. Enzyme Microb Technol 46:526–533. doi:10.1016/j.enzmictec.2010.02.007

    Article  CAS  Google Scholar 

  • Liu C, Hwang C, Liao C (1999) Medium optimization for glutathione production by Saccharomyces cerevisiae. Proc Biochem 34:17–23. doi:10.1016/S0032-9592(98)00055-7

    Article  CAS  Google Scholar 

  • Lorenz E, Schmacht M, Stahl U, Senz M (2015) Enhanced incorporation yield of cysteine for glutathione overproduction by fed-batch fermentation of Saccharomyces cerevisiae. J Biotechnol 216:131–139. doi:10.1016/j.jbiotec.2015.10.016

    Article  CAS  Google Scholar 

  • Lorenz E, Schmacht M, Senz M (2016) Evaluation of cysteine ethyl ester as efficient inducer for glutathione overproduction in Saccharomyces spp. Enzyme Microb Technol 93–94:122–131. doi:10.1016/j.enzmictec.2016.08.004

    Article  Google Scholar 

  • Lu SC (2009) Regulation of glutathione synthesis. Mol Aspects Med 30:42–59. doi:10.1016/j.mam.2008.05.005

    Article  CAS  Google Scholar 

  • Lu SC (2013) Glutathione synthesis. Biochim Biophys Acta 1830:3143–3153. doi:10.1016/j.bbagen.2012.09.008

    Article  CAS  Google Scholar 

  • Lyu C (2016) Rice noodles capable of nourishing faces and protecting skins and preparation method of rice noodles. China Patent Application CN105410629 (A)

  • Mao J, Xu J, Liu S (2016) Fruit wine yeast with high yield of glutathione and application of fruit wine yeast. China Patent Application CN105255748 (A)

  • Marz U (2014) Yeasts, Yeast Extracts, Autolysates and Related Products: The Global Market, Wellesley, MA, USA

  • Meister A (1988) On the discovery of glutathione. Trends Biochem Sci 13:185–188. doi:10.1016/0968-0004(88)90148-X

    Article  CAS  Google Scholar 

  • Meister A, Anderson ME (1983) Glutathione. Annu Rev Biochem 52:711–760. doi:10.1146/annurev.bi.52.070183.003431

    Article  CAS  Google Scholar 

  • Mezzetti F, Vero L de, Giudici P (2014) Evolved Saccharomyces cerevisiae wine strains with enhanced glutathione production obtained by an evolution-based strategy. FEMS Yeast Res 14:977–987. doi:10.1111/1567-1364.12186

    Article  CAS  Google Scholar 

  • Musatti A, Manzoni M, Rollini M (2013) Post-fermentative production of glutathione by baker’s yeast (S. cerevisiae) in compressed and dried forms. N Biotechnol 30:219–226. doi:10.1016/j.nbt.2012.05.024

    Article  CAS  Google Scholar 

  • Musatti A, Devesa V, Calatayud M, Vélez D, Manzoni M, Rollini M (2014) Glutathione-enriched baker’s yeast: production, bioaccessibility and intestinal transport assays. J Appl Microbiol 116:304–313. doi:10.1111/jam.12363

    Article  CAS  Google Scholar 

  • Nakagawa T, Kaji N, Tokuriki M (2016) Use of yeast extract including glutathione as melanin production inhibitor. Taiwan Patent Application TW201620396 (A)

  • Nie M, Wei G, Shao N, Ge X (2010) A novel strategy on the high-cell-density cultivation of Candida utilis for the enhanced production of glutathione. Korean J Chem Eng 27:1246–1251. doi:10.1007/s11814-010-0190-y

    Article  CAS  Google Scholar 

  • Nisamedtinov I, Kevvai K, Orumets K, Rautio JJ, Paalme T (2010) Glutathione accumulation in ethanol-stat fed-batch culture of Saccharomyces cerevisiae with a switch to cysteine feeding. Appl Microbiol Biotechnol 87:175–183. doi:10.1007/s00253-010-2502-x

    Article  CAS  Google Scholar 

  • Noordam B (2013) Process for producing cysteine and/or glutathione from cystine employing yeast. South Africa Patent ZA201202077 (B)

  • Ortiz-Julien A (2012) Method for preventing defective ageing of white wines. United States Patent US8268372 (B2)

  • Orumets K, Kevvai K, Nisamedtinov I, Tamm T, Paalme T (2012) YAP1 over-expression in Saccharomyces cerevisiae enhances glutathione accumulation at its biosynthesis and substrate availability levels. Biotechnol J 7:566–568. doi:10.1002/biot.201100363

    Article  CAS  Google Scholar 

  • Patzschke A, Steiger MG, Holz C, Lang C, Mattanovich D, Sauer M (2015) Enhanced glutathione production by evolutionary engineering of Saccharomyces cerevisiae strains. Biotechnol J 10:1719–1726. doi:10.1002/biot.201400809

    Article  CAS  Google Scholar 

  • Pei J, Huang L (2012) Yeast strain for producing astaxanthin and glutathione by fermentation method and production process thereof. China Patent CN101921712 (B)

  • Perricone C, Carolis C de, Perricone R (2009) Glutathione: a key player in autoimmunity. Autoimmun Rev 8:697–701. doi:10.1016/j.autrev.2009.02.020

    Article  CAS  Google Scholar 

  • Perrone GG, Dawes IW, Grant CM (2005) Glutathione production. United States Patent Application US2005/0239164 (A1)

  • Qian W, Xie H, Wu Q (2016) Method for preparing yeast fusants and screening glutathione high-yield strains. China Patent Application CN105838706 (A)

  • Qijiu C (2011) Culture medium composite used for culturing glutathione productive yeast. China Patent Application CN102134556 (A)

  • Richie JP, Nichenametla S, Neidig W, Calcagnotto A, Haley JS, Schell TD, Muscat JE (2015) Randomized controlled trial of oral glutathione supplementation on body stores of glutathione. Eur J Nutr 54:251–263. doi:10.1007/s00394-014-0706-z

    Article  CAS  Google Scholar 

  • Rodríguez-Bencomo JJ, Andújar-Ortiz I, Moreno-Arribas MV, Simó C, González J, Chana A, Dávalos J, Pozo-Bayón MÁ (2014) Impact of glutathione-enriched inactive dry yeast preparations on the stability of terpenes during model wine aging. J Agric Food Chem 62:1373–1383. doi:10.1021/jf402866q

    Article  Google Scholar 

  • Rollini M, Manzoni M (2006) Influence of different fermentation parameters on glutathione volumetric productivity by Saccharomyces cerevisiae. Proc Biochem 41:1501–1505. doi:10.1016/j.procbio.2006.02.011

    Article  CAS  Google Scholar 

  • Rollini M, Musatti A, Manzoni M (2010) Production of glutathione in extracellular form by Saccharomyces cerevisiae. Proc Biochem 45:441–445. doi:10.1016/j.procbio.2009.10.016

    Article  CAS  Google Scholar 

  • Sakato K, Tanaka H (1992) Advanced control of glutathione fermentation process. Biotechnol Bioeng. doi:10.1002/bit.260400806

    Google Scholar 

  • Santos LO, Gonzales TA, Ubeda BT, Monte Alegre R (2007) Influence of culture conditions on glutathione production by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 77:763–769. doi:10.1007/s00253-007-1211-6

    Article  CAS  Google Scholar 

  • Saucedo AC, Ambati BK (2016) Eye health supplement. United States Patent Application US20160030502 (A1)

  • Schmacht M, Lorenz E, Stahl U, Senz M (2015) Glutathione overproduction in high cell density continuous cultivation of Saccharomyces spp., 28th International VH-Yeast Conference, Berlin, Germany

  • Schmacht M, Lorenz E, Stahl U, Senz M (2017) Medium optimization based on yeast’s elemental composition for glutathione production in Saccharomyces cerevisiae. J Biosci Bioeng. doi:10.1016/j.jbiosc.2016.12.011

    Google Scholar 

  • Schmitt B, Vicenzi M, Garrel C, Denis FM (2015) Effects of N-acetylcysteine, oral glutathione (GSH) and a novel sublingual form of GSH on oxidative stress markers: a comparative crossover study. Redox Biol 6:198–205. doi:10.1016/j.redox.2015.07.012

    Article  CAS  Google Scholar 

  • Shang F, Wang Z, Tan T (2008) High-cell-density cultivation for co-production of ergosterol and reduced glutathione by Saccharomyces cerevisiae. Appl Microbiol Biotechnol 77:1233–1240. doi:10.1007/s00253-007-1272-6

    Article  CAS  Google Scholar 

  • Sonnleitner B, Käppeli O (1986) Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: Formulation and verification of a hypothesis. Biotechnol Bioeng 28:927–937. doi:10.1002/bit.260280620

    Article  CAS  Google Scholar 

  • Stephen DWS, Jamieson DJ (1997) Amino acid-dependent regulation of the Saccharomyces cerevisiae GSH1 gene by hydrogen peroxide. Mol Microbiol 23:203–210. doi:10.1046/j.1365-2958.1997.2081572.x

    Article  CAS  Google Scholar 

  • Suas M (2008) Advanced bread and pastry. Cengage Learning, Boston

    Google Scholar 

  • Suzuki T, Yoshida S, Tsuji S, Ikejima E, Nakajima K, Ikushima S (2014) Highly glutathione-producing yeast and utilization thereof. Japan Patent JP5634051 (B2)

  • Taskin M (2013) A new strategy for improved glutathione production from Saccharomyces cerevisiae: use of cysteine- and glycine-rich chicken feather protein hydrolysate as a new cheap substrate. J Sci Food Agric 93:535–541. doi:10.1002/jsfa.5818

    Article  CAS  Google Scholar 

  • Thiermann M (2010) Non-surgical method for treating cataracts in mammals including man. United States Patent US7776364 (B2)

  • Tomita Y, Ikushima S, Koeda Y, Tamagawa H (2011) Method for producing yeast rich in glutathione. Japan Patent Application JP2011234645 (A)

  • Townsend DM, Tew KD, Tapiero H (2003) The importance of glutathione in human disease. Biomed Pharmacother 57:145–155. doi:10.1016/S0753-3322(03)00043-X

    Article  CAS  Google Scholar 

  • Ubiyvovk VM, Ananin VM, Malyshev AY, Kang HA, Sibirny AA (2011) Optimization of glutathione production in batch and fed-batch cultures by the wild-type and recombinant strains of the methylotrophic yeast Hansenula polymorpha DL-1. BMC Biotechnol 11:1–12. doi:10.1186/1472-6750-11-8

    Article  Google Scholar 

  • Ueda Y, Yonemitsu M, Tsubuku T, Sakaguchi M, Miyajima R (1997) Flavor characteristics of glutathione in raw and cooked foodstuffs. Biosci Biotechnol Biochem 61:1977–1980. doi:10.1271/bbb.61.1977

    Article  CAS  Google Scholar 

  • Versari S, Villa A, Barenghi L, Bradamente S (2012) Method for the production of extracellular glutathione with high yields. European Patent Application EP2501823 (A1)

  • Wang Z (2014) Whitening cosmetic and preparation method thereof. China Patent Application CN104027293 (A)

  • Wang Q (2016) Chewing gum capable of dispelling freckles and beautifying skin. China Patent Application CN106035968 (A)

  • Wang Z, Tan T, Song J (2007) Effect of amino acids addition and feedback control strategies on the high-cell-density cultivation of Saccharomyces cerevisiae for glutathione production. Proc Biochem 42:108–111. doi:10.1016/j.procbio.2006.07.008

    Article  CAS  Google Scholar 

  • Wang B, Liang G, Zhou Q, Xie J, Mo Y (2010) Combined amino acids modulation with H2O2 stress for glutathione overproduction in Candida utilis. Afr J Biotechnol 9:5399–5406. doi:10.5897/AJB10.925

    CAS  Google Scholar 

  • Wang M, Sun J, Xue F, Shang F, Wang Z, Tan T (2012a) The effect of intracellular amino acids on GSH production by high-cell-density cultivation of Saccharomyces cerevisiae. Appl Biochem Biotechnol 168:198–205. doi:10.1007/s12010-011-9435-4

    Article  CAS  Google Scholar 

  • Wang Y, Wang D, Wei G, Shao N (2012b) Enhanced co-production of S-adenosylmethionine and glutathione by an ATP-oriented amino acid addition strategy. Bioresour Technol 107:19–24. doi:10.1016/j.biortech.2011.12.030

    Article  CAS  Google Scholar 

  • Wang F, Dong K, Chen X, Zhu X (2013a) Yeast engineering bacterial strain capable of producing glutathione and application thereof to production of glutathione. China Patent CN102559529 (B)

  • Wang Y, Wang D, Wei G, Wang C (2013b) Improved co-production of S-adenosylmethionine and glutathione using citrate as an auxiliary energy substrate. Bioresour Technol 131:28–32. doi:10.1016/j.biortech.2012.10.168

    Article  CAS  Google Scholar 

  • Wang C, Zhang J, Wu H, Li Z, Ye Q (2015) Heterologous gshF gene expression in various vector systems in Escherichia coli for enhanced glutathione production. J Biotechnol 214:63–68. doi:10.1016/j.jbiotec.2015.09.004

    Article  CAS  Google Scholar 

  • Wang D, Wang C, Wu H, Li Z, Ye Q (2016) Glutathione production by recombinant Escherichia coli expressing bifunctional glutathione synthetase. J Ind Microbiol Biotechnol 43:45–53. doi:10.1007/s10295-015-1707-5

    Article  CAS  Google Scholar 

  • Watanabe F, Hashizume E, Chan GP, Kamimura A (2014) Skin-whitening and skin-condition-improving effects of topical oxidized glutathione: a double-blind and placebo-controlled clinical trial in healthy women. Clin Cosmet Investig Dermatol 7:267–274. doi:10.2147/CCID.S68424

    Article  CAS  Google Scholar 

  • Wei G, Li Y, Du G, Chen J (2003) Application of a two-stage temperature control strategy for enhanced glutathione production in the batch fermentation by Candida utilis. Biotechnol Lett 25:887–890. doi:10.1023/A:1024034508136

    Article  CAS  Google Scholar 

  • Wei G, Wang D, Chen J (2008) Overproduction of Glutathione by L-cystein addition and a temperature-shift strategy. Biotechnol Bioprocess Eng 13:347–353. doi:10.1007/s12257-007-0191-9

    Article  CAS  Google Scholar 

  • Wen S, Zhang T, Tan T (2004) Utilization of amino acids to enhance glutathione production in Saccharomyces cerevisiae. Enzyme Microb Technol 35:501–507. doi:10.1016/j.enzmictec.2004.08.003

    Article  CAS  Google Scholar 

  • Wen S, Zhang T, Tan T (2005) Optimization of the amino acid composition in glutathione fermentation. Proc Biochem 40:3474–3479. doi:10.1016/j.procbio.2005.02.027

    Article  CAS  Google Scholar 

  • Wen S, Zhang T, Tan T (2006) Maximizing production of glutathione by amino acid modulation and high-cell-density fed-batch culture of Saccharomyces cerevisiae. Proc Biochem 41:2424–2428. doi:10.1016/j.procbio.2006.06.030

    Article  CAS  Google Scholar 

  • Wieser H (2007) Chemistry of gluten proteins. Food Microbiol 24:115–119. doi:10.1016/j.fm.2006.07.004

    Article  CAS  Google Scholar 

  • Witschi A, Reddy S, Stofer B, Lauterburg BH (1992) The systemic availability of oral glutathione. Eur J Clin Pharmacol 43:667–669. doi:10.1007/BF02284971

    Article  CAS  Google Scholar 

  • Wu D, Meydani SN, Sastre J, Hayek M, Meydani M (1994) In vitro glutathione supplementation enhances interleukin-2 production and mitogenic response of peripheral blood mononuclear cells from young and old subjects. J Nutr 124:655–663

    CAS  Google Scholar 

  • Xia X, Yang H, Zhu X, Zhang L, Wang W (2013) Production method of yellow rice wine rich in reduced glutathione, and produced yellow rice wine. China Patent CN102492591 (B)

  • Xiong Z, Guo M, Guo Y, Chu J, Zhuang Y, Zhang S (2008) Real-time viable-cell mass monitoring in high-cell-density fed-batch glutathione fermentation by Saccharomyces cerevisiae T65 in industrial complex medium. J Biosci Bioeng 105:409–413. doi:10.1263/jbb.105.409

    Article  CAS  Google Scholar 

  • Xiong Z, Guo M, Guo Y, Chu J, Zhuang Y, Wang NS, Zhang S (2010) RQ feedback control for simultaneous improvement of GSH yield and GSH content in Saccharomyces cerevisiae T65. Enzyme Microb Technol 46:598–602. doi:10.1016/j.enzmictec.2010.03.003

    Article  CAS  Google Scholar 

  • Xiong Z, Guo M, Chu J, Zhuang Y, Zhang S (2015) On-line specific growth rate control for improving reduced glutathione production in Saccharomyces cerevisiae. Biotechnol Bioprocess Eng 20:887–893. doi:10.1007/s12257-015-0018-z

    Article  CAS  Google Scholar 

  • Xu G, Zhang L, Chen Y, Cheng W, Guo Y, Wei Y, Liang J, Tan W (2015) Saccharomyces cerevisiae microbial preparation with high yield of glutathione and preparation method thereof. China Patent Application CN104286415 (A)

  • Xu Z, Yang X, Hang B, Chen B, Li J, Huang L (2016) Mutant gene of gshF genes of Streptococcus agalactiae and application thereof. China Patent Application CN105238797 (A)

  • Ye C, Liu Y, Wang Y, Li H, Wang K (2016) Glutathione beautifying yogurt and production method thereof. China Patent Application CN105685226 (A)

  • Yin H, Ma Y, Deng Y, Xu Z, Liu J, Zhao J, Dong J, Yu J, Chang Z (2016) Genome shuffling of Saccharomyces cerevisiae for enhanced glutathione yield and relative gene expression analysis using fluorescent quantitation reverse transcription polymerase chain reaction. J Microbiol Methods 127:188–192. doi:10.1016/j.mimet.2016.06.012

    Article  CAS  Google Scholar 

  • Yoshida H, Arai S, Hara KY, Yamada R, Ogino C, Fukuda H, Kondo A (2011) Efficient and direct glutathione production from raw starch using engineered Saccharomyces cerevisiae. Appl Microbiol Biotechnol 89:1417–1422. doi:10.1007/s00253-010-2968-6

    Article  CAS  Google Scholar 

  • Zarka MH, Bridge WJ (2017) Oral administration of γ-glutamylcysteine increases intracellular glutathione levels above homeostasis in a randomised human trial pilot study. Redox Biol 11:631–636. doi:10.1016/j.redox.2017.01.014

    Article  CAS  Google Scholar 

  • Zhang Q (2016) Nutrient porridge capable of beautifying features and protecting skin. China Patent Application CN105433203 (A)

  • Zhang J, Greasham R (1999) Chemically defined media for commercial fermentations. Appl Microbiol Biotechnol 51:407–421. doi:10.1007/s002530051411

    Article  CAS  Google Scholar 

  • Zhang T, Wen S, Tan T (2007) Optimization of the medium for glutathione production in Saccharomyces cerevisiae. Proc Biochem 42:454–458. doi:10.1016/j.procbio.2006.09.003

    Article  CAS  Google Scholar 

  • Zhang J, Quan C, Wang C, Wu H, Li Z, Ye Q (2016) Systematic manipulation of glutathione metabolism in Escherichia coli for improved glutathione production. Microb Cell Fact 15:38. doi:10.1186/s12934-016-0439-1

    Article  Google Scholar 

  • Zhang X, Wu H, Huang B, Li Z, Ye Q (2017) One-pot synthesis of glutathione by a two-enzyme cascade using a thermophilic ATP regeneration system. J Biotechnol 241:163–169. doi:10.1016/j.jbiotec.2016.11.034

    Article  CAS  Google Scholar 

  • Zhu H, Huang Y (2014) Method for synthesizing glutathione through fermentation. China Patent Application CN103,695,506 (A)

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Correspondence to Martin Senz.

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Maximilian Schmacht and Eric Lorenz have contributed equally to this article.

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Schmacht, M., Lorenz, E. & Senz, M. Microbial production of glutathione. World J Microbiol Biotechnol 33, 106 (2017). https://doi.org/10.1007/s11274-017-2277-7

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