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Gene Review

GRE3  -  trifunctional aldehyde reductase/xylose...

Saccharomyces cerevisiae S288c

Synonyms: Genes de respuesta a estres protein 3, NADPH-dependent aldo-keto reductase GRE3, NADPH-dependent aldose reductase GRE3, NADPH-dependent methylglyoxal reductase GRE3, Xylose reductase, ...
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Disease relevance of GRE3


High impact information on GRE3

  • A sudden overaccumulation of methylglyoxal (MG) induces, in Saccharomyces cerevisiae, the expression of MG-protective genes, including GPD1, GLO1 and GRE3 [2].
  • Xylose reductase (XR; AKR2B5) is an unusual member of aldo-keto reductase superfamily, because it is one of the few able to efficiently utilize both NADPH and NADH as co-substrates in converting xylose into xylitol [3].
  • Structure-reactivity correlations reveal active-site homologies among NADPH-specific and dual NADPH/NADH-specific yeast xylose reductases and across two aldo/keto reductase families in spite of the phylogenetic separation of the host organisms producing xylose reductase (family 2B) and aldehyde reductase (family 1A) [4].
  • The structures of the Candida tenuis xylose reductase apo- and holoenzyme, which crystallize in spacegroup C2 with different unit cells, have been determined to 2.2 A resolution and an R-factor of 17.9 and 20.8%, respectively [5].
  • Kinetic substituent effects have been used to examine the catalytic reaction profile of xylose reductase from the yeast Candida tenuis, a representative aldo/keto reductase of primary carbohydrate metabolism [4].

Biological context of GRE3

  • Saccharomyces cerevisiae mutants, in which open reading frames (ORFs) displaying similarity to the aldo-keto reductase GRE3 gene have been deleted, were investigated regarding their ability to utilize xylose and arabinose [6].
  • Despite its low XI activity, TMB 3050 was capable of aerobic xylose growth and anaerobic ethanol production at 30 degrees C. The aerobic xylose growth rate reached 0.17 l/h when XI was replaced with xylose reductase (XR) and xylitol dehydrogenase (XDH) genes expressed from a multicopy plasmid, demonstrating that the screening system was functional [7].
  • Biomass was reduced by 31% in strains where GRE3 was deleted, suggesting that fine-tuning of GRE3 expression is the preferred choice rather than deletion [8].
  • A P. stipitis cDNA library in lambda gt11 was screened using antisera against P. stipitis xylose reductase and xylitol dehydrogenase, respectively [9].
  • However, the nucleotide sequence immediately adjacent to the initiation codon of XR, which controls the translation of the gene product, seemed to be five times less effective than the corresponding sequence of the ADC1 gene [10].

Anatomical context of GRE3

  • At low temperatures, the xylose reductase was expressed in soluble and active form up to about 10% of the soluble protein; with rising temperatures formation of visible inclusion bodies occurred [1].

Associations of GRE3 with chemical compounds

  • We found that S. cerevisiae can grow on D-xylose when only the endogenous genes GRE3 (YHR104w), coding for a nonspecific aldose reductase, and XYL2 (YLR070c, ScXYL2), coding for a xylitol dehydrogenase (XDH), are overexpressed under endogenous promoters [11].
  • Overexpression of the GRE3 and ScXYL2 genes in the S. cerevisiae CEN.PK2 strain resulted in a growth rate of 0.01 g of cell dry mass liter(-1) h(-1) and a xylitol yield of 55% when xylose was the main carbon source [11].
  • Finally, induction of GPD1, TPS1 and GRE3, and enhanced MG contents were also observed in low-glucose-growing cells subjected to a sudden increase in glucose availability [12].
  • Both the D-xylose reductase and the L-arabinose reductase activities exclusively used NADPH as co-factor [6].
  • Deletion of the GRE3 gene combined with expression of the xylA gene from T. thermophilus on a replicative plasmid generated recombinant xylose utilizing S. cerevisiae strain TMB3102, which produced ethanol from xylose with a yield of 0.28 mmol of C from ethanol/mmol of C from xylose [13].

Regulatory relationships of GRE3

  • Xylulokinase overexpression in two strains of Saccharomyces cerevisiae also expressing xylose reductase and xylitol dehydrogenase and its effect on fermentation of xylose and lignocellulosic hydrolysate [14].
  • The highest XR or XDH activities were obtained when the expressed gene was controlled by the PGK promoter and located downstream after the ADHI promoter-gene-terminator sequence [15].
  • The mutagenized XYL2 gene could still mediate growth of Saccharomyces cerevisiae transformants on xylose minimal-medium plates when expressed together with the xylose reductase gene (XYL1) [16].

Other interactions of GRE3

  • Increased xylose and arabinose reductase activity was observed in cell extracts for S. cerevisiae overexpressing the GRE3, YPR1 and YJR096w genes [6].
  • These genes, named GRE1, GRE2 and GRE3, were identified by the differential display technique using total RNAs obtained from yeast grown under hyperosmotic conditions [17].
  • The strain expressed XR, XDH, and XK activities of 0.4 to 0.5, 2.7 to 3.4, and 1.5 to 1.7 U/mg, respectively, and was stable for more than 40 generations in continuous fermentations [18].
  • Autoselective xylose-utilising strains of Saccharomyces cerevisiae expressing the xylose reductase (XYL1) and xylitol dehydrogenase (XYL2) genes of Pichia stipitis were constructed by replacing the chromosomal FUR1 gene with a disrupted fur1::LEU2 allele [19].
  • In the ZWF1-disrupted background, the increase in XR activity fully restored the xylose consumption rate [20].

Analytical, diagnostic and therapeutic context of GRE3


  1. Xylose utilisation: cloning and characterisation of the Xylose reductase from Candida tenuis. Häcker, B., Habenicht, A., Kiess, M., Mattes, R. Biol. Chem. (1999) [Pubmed]
  2. The HOG MAP kinase pathway is required for the induction of methylglyoxal-responsive genes and determines methylglyoxal resistance in Saccharomyces cerevisiae. Aguilera, J., Rodríguez-Vargas, S., Prieto, J.A. Mol. Microbiol. (2005) [Pubmed]
  3. Structure of xylose reductase bound to NAD+ and the basis for single and dual co-substrate specificity in family 2 aldo-keto reductases. Kavanagh, K.L., Klimacek, M., Nidetzky, B., Wilson, D.K. Biochem. J. (2003) [Pubmed]
  4. Catalytic reaction profile for NADH-dependent reduction of aromatic aldehydes by xylose reductase from Candida tenuis. Mayr, P., Nidetzky, B. Biochem. J. (2002) [Pubmed]
  5. The structure of apo and holo forms of xylose reductase, a dimeric aldo-keto reductase from Candida tenuis. Kavanagh, K.L., Klimacek, M., Nidetzky, B., Wilson, D.K. Biochemistry (2002) [Pubmed]
  6. Putative xylose and arabinose reductases in Saccharomyces cerevisiae. Träff, K.L., Jönsson, L.J., Hahn-Hägerdal, B. Yeast (2002) [Pubmed]
  7. Investigation of limiting metabolic steps in the utilization of xylose by recombinant Saccharomyces cerevisiae using metabolic engineering. Karhumaa, K., Hahn-Hägerdal, B., Gorwa-Grauslund, M.F. Yeast (2005) [Pubmed]
  8. Endogenous NADPH-dependent aldose reductase activity influences product formation during xylose consumption in recombinant Saccharomyces cerevisiae. Träff-Bjerre, K.L., Jeppsson, M., Hahn-Hägerdal, B., Gorwa-Grauslund, M.F. Yeast (2004) [Pubmed]
  9. Isolation and characterization of the Pichia stipitis xylitol dehydrogenase gene, XYL2, and construction of a xylose-utilizing Saccharomyces cerevisiae transformant. Kötter, P., Amore, R., Hollenberg, C.P., Ciriacy, M. Curr. Genet. (1990) [Pubmed]
  10. Cloning and improving the expression of Pichia stipitis xylose reductase gene in Saccharomyces cerevisiae. Chen, Z., Ho, N.W. Appl. Biochem. Biotechnol. (1993) [Pubmed]
  11. Endogenous xylose pathway in Saccharomyces cerevisiae. Toivari, M.H., Salusjärvi, L., Ruohonen, L., Penttilä, M. Appl. Environ. Microbiol. (2004) [Pubmed]
  12. Yeast cells display a regulatory mechanism in response to methylglyoxal. Aguilera, J., Prieto, J.A. FEMS Yeast Res. (2004) [Pubmed]
  13. Deletion of the GRE3 aldose reductase gene and its influence on xylose metabolism in recombinant strains of Saccharomyces cerevisiae expressing the xylA and XKS1 genes. Träff, K.L., Otero Cordero, R.R., van Zyl, W.H., Hahn-Hägerdal, B. Appl. Environ. Microbiol. (2001) [Pubmed]
  14. Xylulokinase overexpression in two strains of Saccharomyces cerevisiae also expressing xylose reductase and xylitol dehydrogenase and its effect on fermentation of xylose and lignocellulosic hydrolysate. Johansson, B., Christensson, C., Hobley, T., Hahn-Hägerdal, B. Appl. Environ. Microbiol. (2001) [Pubmed]
  15. Effect on product formation in recombinant Saccharomyces cerevisiae strains expressing different levels of xylose metabolic genes. Bao, X., Gao, D., Qu, Y., Wang, Z., Walfridssion, M., Hahn-Hagerbal, B. Chin. J. Biotechnol. (1997) [Pubmed]
  16. Amino acid substitutions in the yeast Pichia stipitis xylitol dehydrogenase coenzyme-binding domain affect the coenzyme specificity. Metzger, M.H., Hollenberg, C.P. Eur. J. Biochem. (1995) [Pubmed]
  17. Three genes whose expression is induced by stress in Saccharomyces cerevisiae. Garay-Arroyo, A., Covarrubias, A.A. Yeast (1999) [Pubmed]
  18. Anaerobic xylose fermentation by recombinant Saccharomyces cerevisiae carrying XYL1, XYL2, and XKS1 in mineral medium chemostat cultures. Eliasson, A., Christensson, C., Wahlbom, C.F., Hahn-Hägerdal, B. Appl. Environ. Microbiol. (2000) [Pubmed]
  19. Xylose utilisation by recombinant strains of Saccharomyces cerevisiae on different carbon sources. van Zyl, W.H., Eliasson, A., Hobley, T., Hahn-Hägerdal, B. Appl. Microbiol. Biotechnol. (1999) [Pubmed]
  20. Effect of enhanced xylose reductase activity on xylose consumption and product distribution in xylose-fermenting recombinant Saccharomyces cerevisiae. Jeppsson, M., Träff, K., Johansson, B., Hahn-Hägerdal, B., Gorwa-Grauslund, M.F. FEMS Yeast Res. (2003) [Pubmed]
  21. Properties of the NAD(P)H-dependent xylose reductase from the xylose-fermenting yeast Pichia stipitis. Verduyn, C., Van Kleef, R., Frank, J., Schreuder, H., Van Dijken, J.P., Scheffers, W.A. Biochem. J. (1985) [Pubmed]
  22. Exploring the active site of yeast xylose reductase by site-directed mutagenesis of sequence motifs characteristic of two dehydrogenase/reductase family types. Klimacek, M., Szekely, M., Griessler, R., Nidetzky, B. FEBS Lett. (2001) [Pubmed]
  23. Isolation and characterization of the gene encoding xylose reductase from Kluyveromyces lactis. Billard, P., Ménart, S., Fleer, R., Bolotin-Fukuhara, M. Gene (1995) [Pubmed]
  24. Xylitol production by recombinant Saccharomyces cerevisiae expressing the Pichia stipitis and Candida shehatae XYL1 genes. Govinden, R., Pillay, B., van Zyl, W.H., Pillay, D. Appl. Microbiol. Biotechnol. (2001) [Pubmed]
  25. The coenzyme specificity of Candida tenuis xylose reductase (AKR2B5) explored by site-directed mutagenesis and X-ray crystallography. Petschacher, B., Leitgeb, S., Kavanagh, K.L., Wilson, D.K., Nidetzky, B. Biochem. J. (2005) [Pubmed]
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