ISSN 2074-9414 (Print),
ISSN 2313-1748 (Online)

Yeasts as a Glutathione Producer

Abstract
Introduction. Yeast is a fast-growing single-celled microorganism and an inexpensive source of various biologically active substances, such as antioxidants, e.g. Glutathione (GSH). Antioxidant properties are determined by the presence of sulfhydryl group. The global demand for glutathione is estimated to exceed 9 billion USD at the expense not only of pure crystalized glutathione, but also of glutathione-enriched yeast extracts. In the food industry, glutathione is used to improve the quality of the dough and enhance the taste of various products. The present research featured domestic and foreign studies on the content of glutathione in yeast, methods of biosynthesis, and antioxidant properties. Results and discussion. The content of glutathione ranges from 0.1 to 1% per completely dry biomass (CDB) in wild yeast strains. The fermentative method for the accumulation of glutathione is based on the optimization of the nutrient medium and the use of glutathione precursors, i.e. cysteine, glutamic acid, and glycine. Thus, this method makes it possible to double the content of intracellular glutathione in certain cultivation conditions. The use of non-directed mutagenesis methods can increase glutathione synthesis up to 5% in separate mutant strains, although the mechanism of synthesis is not always clear under such conditions. However, up to 2.27% of glutathione is being formed under directed change of the genome. In addition, the level of glutathione in cells increases under the influence of certain physical factors. For example, glutathione biosynthesis increases by 39% if yeast is exposed to a magnetic field. The enzymatic method requires maintaining the following factors: the presence of precursors (L-glutamic acid, L-cysteine, glycine), ATP, Mg2+ ions to activate GSH1 and GSH2, the pH of the medium, and the introduction of the necessary enzymes into the bioreactor. Hiwever, this method is non-economically profitable in large scale productions due to the needs in use ATP. Conclusion. The survey research demonstrated the effect of technological characteristics of cultivation and biotechnological properties of Saccharomyces cerevisiae on the accumulation of glutathione.
Keywords
Fungi, Saccharomyces cerevisiae, oligopeptides, cultivation, antioxidative activity
REFERENCES
  1. Manal FM, Thalooth AT, Essa REY, Mirvat EG. The stimulatory effects of Tryptophan and yeast on yield and nutrient status of Wheat plants (Triticum aestivum) grown in newly reclaimed soil. Middle East Journal of Agriculture Research. 2018;7(1):27–33.
  2. Chang C-L, Kao T-H. Antiobesity effect of brewer’s yeast biomass in animal model. Journal of Functional Foods. 2019;55:255–262. DOI: https://doi.org/10.1016/j.jff.2019.02.027.
  3. Wu G. Amino Acids: Biochemistry and Nutrition. New York: CRC Press; 2013. pp. 140–150.
  4. Alanazi AM, Mostafa GAE, Al-Badr AA. Chapter two – glutathione. Profiles of Drug Substances, Excipients and Related Methodology. 2015;40:43–158. DOI: https://doi.org/10.1016/bs.podrm.2015.02.001.
  5. Oztürk S, Cerit I, Mutlu S, Demirkol O. Enrichment of cookies with glutathione by inactive yeast cells (Saccharomyces cerevisiae): Physicochemical and functional properties. Journal of Cereal Science. 2017;78:19–24. DOI: https://doi.org/10.1016/j.jcs.2017.06.019.
  6. Penninckx MJ. An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Research. 2002;2(3):295–305. DOI: https://doi.org/10.1016/S1567-1356(02)00081-8.
  7. Gümüsay OA, Borazan AA, Ercal N, Demirkol O. Drying effects on the antioxidant properties of tomatoes and ginger. Food Chemistry. 2015;173:156–162. DOI: https://doi.org/10.1016/j.foodchem.2014.09.162.
  8. Suzuki T, Yokoyama A, Tsuji T, Ikeshima E, Nakashima K, Ikushima S, et al. Identification and characterization of genes involved in glutathione production in yeast. Journal of Bioscience and Bioengineering. 2011;112(2):107–113. DOI: https://doi.org/10.1016/j.jbiosc.2011.04.007.
  9. Kulaeva OA, Tsyganov VYe. Gene expression analysis of genes coding key enzymes of cadmium detoxification in garden pea symbiotic nodules. Ekologicheskaya Genetika. 2014;12(2):13–22. (In Russ.).
  10. Lu SC. Regulation of glutathione synthesis. Molecular Aspects of Medicine. 2009;30(1–2):42–59. DOI: https://doi.org/10.1016/j.mam.2008.05.005.
  11. Nikitin AV, Zolotareva MA. The role of the enzyme activity in formation of oxidative stress in the patients with bronchial asthma (review). Journal of New Medical Technologies. 2013;20(2):165–169. (In Russ.).
  12. Lu SC. Glutathione synthesis. Biochimica et Biophysica Acta (BBA) – General Subjects. 2013;1830(5):3143–3153. DOI: https://doi.org/10.1016/j.bbagen.2012.09.008.
  13. Li Y, Wei G, Chen J. Glutathione: a review on biotechnological production. Applied Microbiology and Biotechnology. 2004;66(3):233–242. DOI: https://doi.org/10.1007/s00253-004-1751-y.
  14. Li W, Li Z, Ye Q. Enzymatic synthesis of glutathione using yeast cells in two-stage reaction. Bioprocess and Biosystems Engineering. 2010;33(6):675–682. DOI: https://doi.org/10.1007/s00449-009-0361-6.
  15. Annemüller G, Manger H-J, Lietz P. The yeast in the brewery. Management. Pure yeast cultures. Propagation. Berlin: VLB Berlin; 2011. 440 p.
  16. Ask M, Mapelli V, Höck H, Olsson L, Bettiga M. Engineering glutathione biosynthesis of Saccharomyces cerevisiae increases robustness to inhibitors in pretreated lignocellulosic materials. Microbial Cell Factories. 2013;12(1). DOI: https://doi.org/10.1186/1475-2859-12-87.
  17. Hamad GM, Taha TH, Alshehri AM, Hafez EE. Enhancement of the glutathione production by mutated yeast strains and its potential as food supplement and preservative. 2018;13(1):28–36. DOI: https://doi.org/10.3923/jm.2018.28.36.
  18. Wang Z-Y, He X-P, Liu N, Zhang B-R. Construction of self-cloning industrial brewing yeast with high-glutathione and low-diacetyl production. International Journal of Food Science and Technology. 2008;4(6):989–994. DOI: https://doi.org/10.1111/j.1365-2621.2007.01546.x.
  19. Sasaki K, Hara KY, Kawaguchi H, Sazuka T, Ogino C, Kondo A. Nanofiltration concentration of extracellular glutathione produced by engineered Saccharomyces cerevisiae. Journal of Bioscience and Bioengineering. 2016;121(1):96–100. DOI: https://doi.org/10.1016/j.jbiosc.2015.05.013.
  20. Prima A, Hara KY, Djohan AC, Kashiwagi N, Kahar P, Ishii J, et al. Glutathione production from mannan-based bioresource by mannanase/mannosidase expressing Saccharomyces cerevisiae. Bioresource Technology. 2017;245:1400–1406. DOI: https://doi.org/10.1016/j.biortech.2017.05.190.
  21. Anschau A, dos Santos LO, Alegre RM. A cost effective fermentative production of glutathione by Saccharomyces cerevisiae with cane molasses and glycerol. Brazilian Archives of Biology and Technology. 2013;56(5):849–857. DOI: https://doi.org/10.1590/S1516-89132013000500017.
  22. Cha J-Y, Park J-C, Jeon B-S, Lee Y-C, Cho Y-S. Optimal Fermentation Conditions for Enhanced Glutathione Production by Saccharomyces cerevisiae FF-8. Journal of Microbiology. 2004;42(1):51–55.
  23. Schmacht M, Lorenz E, Stahl U, Senz M. Medium optimization based on yeast’s elemental composition for glutathione production in Saccharomyces cerevisiae. Journal of Bioscience and Bioengineering. 2017;123(5):555–561. DOI: https://doi.org/10.1016/j.jbiosc.2016.12.011.
  24. Musatti A, Manzoni M, Rollini M. Post-fermentative production of glutathione by baker’s yeast (S. cerevisiae) in compressed and dried forms. New Biotechnology. 2013;30(2):219–226. DOI: https://doi.org/10.1016/j.nbt.2012.05.024.
  25. Santos LO, Alegre RM, Garcia-Diego C, Cuellar J. Effects of magnetic fields on biomass and glutathione production by the yeast Saccharomyces cerevisiae. Process Biochemistry. 2010;45(8):1362–1367. DOI: https://doi.org/10.1016/j.procbio.2010.05.008.
  26. Sharipov KO, Skvortsova NN, Arykbayeva AB. The study of the content of glutathione in the yeast Saccharomyces cerevisiae during storage. Vestnik KazNMU. 2017;(3):217–219. (In Russ.).
  27. Skvortsova NN, Shleikin AG, Arykbayeva AB. The effect of prolonged freezing on the content of thiol substances and proteolytic activity of yeast. Journal of International Academy of Refrigeration. 2018;(3):62–66. (In Russ.). DOI: https://doi.org/10.17586/1606-4313-2018-17-3-62-66.
  28. Smirnov LP, Sukhovskaya IV. Glutathione role in antioxidant protection and in functioning of biotransformation system. Proceedings of Petrozavodsk State University. 2014;143(6):34–40. (In Russ.).
  29. Couto N, Wood J, Barber J. The role of glutathione reductase and related enzymes on cellular redox homoeostasis network. Free Radical Biology and Medicine. 2016;95:27–42. DOI: https://doi.org/10.1016/j.freeradbiomed.2016.02.028.
  30. Bilan DS. Geneticheski kodiruemye fluorestsentnye sensory okislitelʹno-vosstanovitelʹnykh protsessov v zhivykh sistemakh [Genetically encoded fluorescence sensors of redox processes in living systems]. Cand. bio. sci. diss. Moscow: Shemyakin and Ovchinnikov Institute of Bioorganic Chemistry of the Russian Academy of Sciences; 2014. 127 p.
  31. Bilan DS, Shokhina AG, Lukyanov SA, Belousov VV. Main cellular redox couples. Russian Journal of Bioorganic Chemistry. 2015;41(4):385–402. (In Russ.). DOI: https://doi.org/10.7868/S0132342315040041.
  32. Kurylenko OO, Dmytruk KV, Sibirny A. Glutathione metabolism in yeasts and construction of the advanced producers of this tripeptide. In: Sibirny A, editor. Non-conventional yeasts: from basic research to application. Cham: Springer; 2019. pp. 153–196. DOI: https://doi.org/https://doi.org/10.1007/978-3-030-21110-3_6.
  33. Kumar C, Sharma R, Bachhawat AK. Utilization of glutathione as an exogenous sulfur source is independent of γ-glutamyl transpeptidase in the yeast Saccharomyces cerevisiae: evidence for an alternative gluathione degradation pathway. FEMS Microbiology Letters. 2003;219(2):187–194. DOI: https://doi.org/10.1016/S0378-1097(03)00059-4.
  34. Schmacht M, Lorenz E, Senz M. Microbial production of glutathione. World Journal of Microbiology and Biotechnology. 2017;33(6). DOI: https://doi.org/10.1007/s11274-017-2277-7.
  35. Wang Z, Tan T, Song J. Effect of amino acids addition and feedback control strategies on the high-cell-density cultivation of Saccharomyces cerevisiae for glutathione production. Process Biochemistry. 2007;42(1):108–111. DOI: https://doi.org/10.1016/j.procbio.2006.07.008.
  36. Wen S, Zhang T, Tan T. Maximizing production of glutathione by amino acid modulation and high-cell-density fedbatch culture of Saccharomyces cerevisiae. Process Biochemistry. 2006;41(12):2424–2428. DOI: https://doi.org/10.1016/j.procbio.2006.06.030.
  37. Tang L, Wang W, Zhou W, Cheng K, Yang Y, Liu M, et al. Three-pathway combination for glutathione biosynthesis in Saccharomyces cerevisiae. Microbial Cell Factories. 2015;14(1). DOI: https://doi.org/10.1186/s12934-015-0327-0.
  38. Lushchak VI. Oxidative stress in yeast. Biochemistry. 2010;75(3):346–364. (In Russ.).
  39. Kerti O. Molecular mechanisms controlling intracellular glutathione levels in baker’s yeast Saccharomyces cerevisiae and a random mutagenized glutathione over-accumulating isolate. Tallinn: Tallinn University of Technology; 2012. 108 p.
How to quote?
Meledina TV, Morozov AA, Davydenko SG, Ternovskoy GV. Yeasts as a Glutathione Producer. Food Processing: Techniques and Technology. 2020;50(1):140–148. (In Russ.). DOI: https://doi.org/10.21603/2074-9414-2020-1-140-148.
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