The role of glutathione in detoxification of chromate by Hansenula (Ogataea) polymorpha yeast

  • D. V. Fedorovych
  • M. T. Yurkiv
  • O. M. Kolodii
  • O. O. Kurylenko
  • D. Grabek-Lejko
  • A. A. Sibirny


Aim. Chromate is very toxic, displays mutagenic and carcinogenic activity and its pollution poses a serious environment problem. The development of efficient methods for detoxification of this oxyanion is of great importance. For microbial cells, it is known that chromate transported in cells can be reduced to less toxic Cr3+. The most powerful chromate reductants could be glutathione (GSH) or cysteine. The role of GSH in detoxification of chromate by the yeast Hansenula polymorpha was evaluated. Methods. For this purpose recombinant strains with overexpressed GSH2 and MET4 genes and mutant defective in GSH biosynthesis were used. Profiles of GSH and chromium contents as well as rate of reduction of chromate were studied in relation to chromate resistance/sensitivity of the wild- type and mutant yeast strains. Results. High level of GSH in recombinant strains of H. polymorpha slightly changed the sensitivity/tolerance to chromate, but increased the rate of reduction of Cr6+ and reduces the amount of chromium accumulated in the cells. Deletion of GSH2 gene, encoding the enzyme of the first reaction of GSH synthesis, leads to increased sensitivity to the action of chromate. Conclusions. GSH can be considered as an important part of chromate detoxification system in H. polymorpha.

Keywords: glutathione, chromium, yeast, chromate reduction, Hansenula (Ogataea) polymorpha.


Penninckx M.J. A short review on the role of glutathione in the response of yeasts to nutritional, environmental, and oxidative stresses. Enzyme Microb.Technol. 2000. V. 26. P. 737-742. doi: 10.1016/S0141-0229(00)00165-4

Penninckx M.J. An overview on glutathione in Saccharomyces versus non-conventional yeasts. FEMS Yeast Res. 2002. V. 2. P. 295-305. doi: 10.1016/S1567-1356(02)00081-8

Lushchak V.I. Glutathione Homeostasis and Functions: Potential Targets for Medical Interventions. Journal of Amino Acids. 2012. doi: 10.1155/2012/736837

Viti C., Marchi E., Decorosi F.,Giovannetti L. Molecular mechanisms of Cr(VI) resistance in bacteria and fungi. FEMS Microbiol. Rev. 2014. V. 38. P. 633-659. doi: 10.1111/1574-6976.12051

Valko M., Morris H., Cronin M.T.D. Metals, toxicity and oxidative stress. Current Medicinal Chemistry. 2005. V. 12. P. 1161-1208. doi: 10.2174/0929867053764635

Gharieb M.M., Gadd G.M. Evidence for the involvement of vacuolar activity in metal(loid) tolerance: vacuolar-lacking and -defective mutants of Saccharomyces cerevisiae display higher sensitivity to chromate, telurite and selenite. BioMetals. 1998. V. 11. P. 101-106.

Ksheminska H., Fedorovych D., Honchar T., Ivash M., Gonchar M. Yeast tolerance to chromium depends on extra-cellular chromate reduction and Cr(III)-chelation. Food Technol. Biotechnol. 2008. V. 46. P. 420-427.

Pesti M., Gazdag Z., Emri T., Farkas N., Koosz Z., Belagyi J., Pocsi I. Chromate sensitivity in fission yeast is caused by increased glutathione reductase activity and peroxide overproduction. J. Basic Microbiol. 2002. V. 42. P.408-419. doi: 10.1002/1521-4028(200212)42:6<408::AID-JOBM408>3.0.CO;2-8

Grabek-Lejko D., Kurylenko O.O., Sibirny V.A., Ubiyvovk V.M., Penninckx M., Sibirny AA. Alcoholic fermentation by wild-type Hansenula polymorpha and Saccharomyces cerevisiae versus recombinant strains with an elevated level of intracellular glutathione. J. Ind. Microbiol. Biotechnol. 2011. V. 38. P. 1853-1859. doi: 10.1007/s10295-011-0974-z

Yurkiv M., Kurylenko O., Vasylyshyn R., Dmytruk K., Sibirny A. Сonstruction of the efficient glutathione producers in the yeast Hansenula рolymorpha. Living Organisms and Bioanalytical Approaches for Detoxification and Monitoring of Toxic Compounds: Monograph / University of Rzeszow. Rzeszow, 2015. P. 323–332.

Ubiyvovk V.M., Blazhenko O.V., Zimmermann M., Sohn M.J., Kang H. A Cloning and functional analysis of the GSH1/MET1 gene complementing cysteine and glutathione auxotrophy of the methylotrophic yeast Hansenula polymorpha. Ukr. Biokhim. Zh. 2011. V. 83. P. 67–81.

Lowry O.H., Rosebrough N.J., Farr A.L., Randall R.J. Protein measurement with a Folin phenol reagent. J. Biol. Chem. 1951. V. 193, N 1. P. 265–275.

Ksheminska H.P., Honchar T.M., Gayda G.Z, Gonchar M.V. Extra-cellular chromate-reducing activity of the yeast cultures. Central European Science Journals. 2006. V. 1. P. 137–149. doi: 10.2478/s11535-006-0009-3.