Functional studies of aldo-keto reductases in Saccharomyces cerevisiae

Chang, Qing; Griest, Terry A.; Harter, Theresa; Petrash, J. Mark

doi:10.1016/j.bbamcr.2006.10.009

Cited by 58 publications

(52 citation statements)

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“…The human aldose reductase is implicated in diabetic complications by the conversion of excess aldoses to sugar alcohols (Chang et al 2007). Due to its ability to reduce glucose, the aldose reductase is involved in several tissue-specific metabolic pathways (Srivastava et al 2005).…”

Section: Introductionmentioning

confidence: 99%

Overproduction of a rice aldo–keto reductase increases oxidative and heat stress tolerance by malondialdehyde and methylglyoxal detoxification

et al. 2011

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The accumulation of toxic compounds generated by the interaction between reactive oxygen species and polyunsaturated fatty acids of membrane lipids can significantly damage plant cells. A plethora of enzymes act on these reactive carbonyls, reducing their toxicity. Based on the chromosomal localization and on their homology with other stress-induced aldo-keto reductases (AKRs) we have selected three rice AKR genes. The transcription level of OsAKR1 was greatly induced by abscisic acid and various stress treatments; the other two AKR genes tested were moderately stress-inducible. The OsAKR1 recombinant protein exhibited a high nicotinamide adenine dinucleotide phosphate-dependent catalytic activity to reduce toxic aldehydes including glycolysis-derived methylglyoxal (MG) and lipid peroxidation-originated malondialdehyde (MDA). The function of this enzyme in MG detoxification was demonstrated in vivo in E. coli and in transgenic plants overproducing the OsAKR1 protein. Heterologous synthesis of the OsAKR1 enzyme in transgenic tobacco plants resulted in increased tolerance against oxidative stress generated by methylviologen (MV) and improved resistance to high temperature. In these plants lower levels of MDA were detected both following MV and heat treatment due to the activity of the OsAKR1 enzyme. The transgenic tobaccos also exhibited higher AKR activity and accumulated less MG in their leaves than the wild type plants; both in the presence and absence of heat stress. These results support the positive role of OsAKR1 in abiotic stress-related reactive aldehyde detoxification pathways and its use for improvement of stress tolerance in plants.

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Section: Introductionmentioning

confidence: 99%

Overproduction of a rice aldo–keto reductase increases oxidative and heat stress tolerance by malondialdehyde and methylglyoxal detoxification

et al. 2011

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“…Among the most upregulated genes in both strains upon furfural increase from 15 to 25 mM were the oxireductases ADH7, GRE2, OYE3, AAD4, YML131W, YDL124W, OYE2, and GCY1 (see Table S1 in the supplemental material). Six of them prefer NADPH as the cofactor (6,7,21,26,33,44), while for AAD4 and YML131W, the cofactor preference is not known (Saccharomyces Genome Database at http://www.yeastgenome.org). This is consistent with our finding that central carbon metabolism doubles the NADPH-generating pentose phosphate pathway fluxes upon 25 mM furfural challenge.…”

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confidence: 99%

“…Generally, metabolic fluxes were determined as described previously (12,52,53). The furfural-containing feed was replaced after at least 5 volume changes by an identical medium containing [1][2][3][4][5][6][7][8][9][10][11][12][13] C]glucose instead of naturally labeled glucose. Samples for metabolic flux analysis were withdrawn after at least 0.7 volume changes with the labeled feed.…”

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confidence: 99%

Resistance of Saccharomyces cerevisiae to High Concentrations of Furfural Is Based on NADPH-Dependent Reduction by at Least Two Oxireductases

Heer

Heine

Sauer

2009

Appl Environ Microbiol

147

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Biofuels derived from lignocellulosic biomass hold promises for a sustainable fuel economy, but several problems hamper their economical feasibility. One important problem is the presence of toxic compounds in processed lignocellulosic hydrolysates, with furfural as a key toxin. While Saccharomyces cerevisiae has some intrinsic ability to reduce furfural to the less-toxic furfuryl alcohol, higher resistance is necessary for process conditions. By comparing an evolved, furfural-resistant strain and its parent in microaerobic, glucose-limited chemostats at increasing furfural challenge, we elucidate key mechanism and the molecular basis of both natural and high-level furfural resistance. At lower concentrations of furfural, NADH-dependent oxireductases are the main defense mechanism. At furfural concentrations above 15 mM, however, 13 C-flux and global array-based transcript analysis demonstrated that the NADPH-generating flux through the pentose phosphate pathway increases and that NADPH-dependent oxireductases become the major resistance mechanism. The transcript analysis further revealed that iron transmembrane transport is upregulated in response to furfural. While these responses occur in both strains, high-level resistance in the evolved strain was based on strong induction of ADH7, the uncharacterized open reading frame (ORF) YKL071W, and four further, likely NADPHdependent, oxireductases. By overexpressing the ADH7 gene and the ORF YKL071W, we inversely engineered significantly increased furfural resistance in the parent strain, thereby demonstrating that these two enzymes are key elements of the resistance phenotype.

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“…The difficulty of this approach is illustrated in Saccharomyces cerevisiae, where only a particular triple knockout of AKR genes, resulted in a glucose-dependent heat shock phenotype which could be rescued by expression of human aldose reductase [48].…”

Section: Discussionmentioning

confidence: 99%

The diversity of microbial aldo/keto reductases from Escherichia coli K12

Lapthorn

Zhu

Ellis

2013

Chemico-Biological Interactions

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reductase, tyrosine auxotrophy suppressor protein, L-glyceraldehyde 3-phosphate reductase, AKR quaternary structure. AbstractThe genome of Escherichia coli K12 contains 9 open reading frames encoding aldo/keto reductases (AKR) that are differentially regulated and sequence diverse. A significant amount of data is available for the E. coli AKRs through the availability of gene knockouts and gene expression studies, which adds to the biochemical and kinetic data.This together with the availability of crystal structures for nearly half of the E. coli AKRs and homologues of several others provides an opportunity to look at the diversity of these representative bacterial AKRs. Based around the common AKR fold of (β/α) 8 barrel with two additional α-helices, the E. coli AKRs have a loop structure that is more diverse than their mammalian counterparts, creating a variety of active site architectures. Nearly half of the AKRs are expected to be monomeric, but there are examples of dimeric, trimeric and octameric enzymes, as well as diversity in specificity for NAD as well as NADP as a cofactor. However in functional assignments and characterisation of enzyme activities there is a paucity of data when compared to the mammalian AKR enzymes. 1.

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Functional studies of aldo-keto reductases in Saccharomyces cerevisiae

Cited by 58 publications

References 58 publications

Overproduction of a rice aldo–keto reductase increases oxidative and heat stress tolerance by malondialdehyde and methylglyoxal detoxification

Overproduction of a rice aldo–keto reductase increases oxidative and heat stress tolerance by malondialdehyde and methylglyoxal detoxification

Resistance of Saccharomyces cerevisiae to High Concentrations of Furfural Is Based on NADPH-Dependent Reduction by at Least Two Oxireductases

The diversity of microbial aldo/keto reductases from Escherichia coli K12

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