A transcriptomic analysis of the response of Saccharomyces cerevisiae to increases in NADPH oxidation [2010]
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ABSTRACT:
ORGANISM(S): Saccharomyces cerevisiae
PROVIDER: GSE34809 | GEO | 2012/04/01
SECONDARY ACCESSION(S): PRJNA156291
REPOSITORIES: GEO
Similar Datasets
Project description:Experience 2: 59A vs. 59A NADH Bdh200 mM, 59A NADPH Bdh200mM and 59A NADPH Bdh300 mM Analysis used RNA samples of three replicates by strain extracted from cells harvested at mid-exponential phase of wine fermentation
2012-03-31 | E-GEOD-34809 | biostudies-arrayexpress
Project description:Experience 1: 59A vs. 59A NADPH Bdh100mM
2012-04-01 | GSE34808 | GEO
Project description:Experience 1: 59A vs. 59A NADPH Bdh100mM Analysis used RNA samples of three independent replicates by strain extracted from cells harvested at mid-exponential phase of oenological fermentation
2012-03-31 | E-GEOD-34808 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE34808: A transcriptomic analysis of the response of Saccharomyces cerevisiae to increases in NADPH oxidation [2009] GSE34809: A transcriptomic analysis of the response of Saccharomyces cerevisiae to increases in NADPH oxidation [2010] Refer to individual Series
2012-03-31 | E-GEOD-34810 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below.
2012-04-01 | GSE34810 | GEO
Project description:Resistance of Saccharomyces cerevisiae to high furfural concentration is based on NADPH-dependent reduction by at least two oxireductases. 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 micro-aerobic, 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 furfural concentrations, NADH-dependent oxireductases are the main defence mechanism. At concentrations above 15 mM, however, [1-13C]-flux and global array-based transcript analysis demonstrated that the NADPH-generating flux through pentose-phosphate pathway increases and that NADPH-dependent oxireductases became the major resistance mechanism. The transcript analysis further revealed that iron transmembrane transport is up-regulated 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 uncharacterised ORF YKL071W and 4 further, likely NADPH-dependent oxireductases. By overexpressing the ADH7 gene and the ORF YKL071W, we inverse engineered significantly increased furfural resistance in the parent strain, thereby demonstrating these two enzymes to be key elements of the resistance phenotype.
2009-09-29 | GSE18314 | GEO
Project description:When the yeast Saccharomyces cerevisiae is subjected to increasing glycolytic fluxes under aerobic conditions, there is a threshold value of the glucose uptake rate at which the metabolism shifts from being purely respiratory to mixed respiratory and fermentative. This shift is characterized by ethanol production, a phenomenon known as the Crabtree effect due to its analogy with lactate overflow in cancer cells. It is well known that at high glycolytic fluxes there is glucose repression of respiratory pathways resulting in a decrease in the respiratory capacity. Despite many years of detailed studies on this subject, it is not known whether the onset of the Crabtree effect (or overflow metabolism) is due to a limited respiratory capacity or caused by glucose-mediated repression of respiration. We addressed this issue by increasing respiration in S. cerevisiae by introducing a heterologous alternative oxidase, and observed reduced aerobic ethanol formation. In contrast, increasing non-respiratory NADH oxidation by overexpression of a water-forming NADH oxidase reduced aerobic glycerol formation. The metabolic response to elevated alternative oxidase occurred predominantly in the mitochondria, while NADH oxidase affected genes that catalyze cytosolic reactions. Moreover, NADH oxidase restored the deficiency of cytosolic NADH dehydrogenases in S. cerevisiae. These results indicate that NADH oxidase localizes in the cytosol, while alternative oxidase is directed to the mitochondria. The onset of aerobic ethanol formation is demonstrated to be a consequence of an imbalance in mitochondrial redox balancing. In addition to answering fundamental physiological questions, our findings are relevant for all biomass derived applications of S. cerevisiae. Keywords: Genetic Modification
2007-02-01 | GSE6277 | GEO
Project description:Resistance of Saccharomyces cerevisiae to high furfural concentration is based on NADPH-dependent reduction by at least two oxireductases. 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 micro-aerobic, 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 furfural concentrations, NADH-dependent oxireductases are the main defence mechanism. At concentrations above 15 mM, however, [1-13C]-flux and global array-based transcript analysis demonstrated that the NADPH-generating flux through pentose-phosphate pathway increases and that NADPH-dependent oxireductases became the major resistance mechanism. The transcript analysis further revealed that iron transmembrane transport is up-regulated 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 uncharacterised ORF YKL071W and 4 further, likely NADPH-dependent oxireductases. By overexpressing the ADH7 gene and the ORF YKL071W, we inverse engineered significantly increased furfural resistance in the parent strain, thereby demonstrating these two enzymes to be key elements of the resistance phenotype. Experiment Overall Design: RNA levels were measured in glucose limited, micro-aerobic chemostat cultures with different concentrations of the growth inhibitor furfural. Two strains were compared: TMB3400-FT30-3 is a strain that has been evolutionary adapted to withstand high furfural concentrations. TMB3400 is its less resistant parent. Number of biological replicates: 2-3.
2009-10-03 | E-GEOD-18314 | biostudies-arrayexpress
Project description:BACKGROUND: Redox homeostasis is essential to sustain metabolism and growth. We recently reported that yeast cells meet a gradual increase in imposed NADPH demand by progressively increasing flux through the pentose phosphate (PP) and acetate pathways and by exchanging NADH for NADPH in the cytosol, via a transhydrogenase-like cycle. Here, we studied the mechanisms underlying this metabolic response, through a combination of gene expression profiling and analyses of extracellular and intracellular metabolites and 13?C-flux analysis. RESULTS: NADPH oxidation was increased by reducing acetoin to 2,3-butanediol in a strain overexpressing an engineered NADPH-dependent butanediol dehydrogenase cultured in the presence of acetoin. An increase in NADPH demand to 22 times the anabolic requirement for NADPH was accompanied by the intracellular accumulation of PP pathway metabolites consistent with an increase in flux through this pathway. Increases in NADPH demand were accompanied by the successive induction of several genes of the PP pathway. NADPH-consuming pathways, such as amino-acid biosynthesis, were upregulated as an indirect effect of the decrease in NADPH availability. Metabolomic analysis showed that the most extreme modification of NADPH demand resulted in an energetic problem. Our results also highlight the influence of redox status on aroma production. CONCLUSIONS: Combined 13?C-flux, intracellular metabolite levels and microarrays analyses revealed that NADPH homeostasis, in response to a progressive increase in NADPH demand, was achieved by the regulation, at several levels, of the PP pathway. This pathway is principally under metabolic control, but regulation of the transcription of PP pathway genes can exert a stronger effect, by redirecting larger amounts of carbon to this pathway to satisfy the demand for NADPH. No coordinated response of genes involved in NADPH metabolism was observed, suggesting that yeast has no system for sensing NADPH/NADP+ ratio. Instead, the induction of NADPH-consuming amino-acid pathways in conditions of NADPH limitation may indirectly trigger the transcription of a set of PP pathway genes.
| S-EPMC3431268 | biostudies-literature
Project description:NADPH has been long well-recognized as a key cofactor for antioxidant defense and reductive biosynthesis. Here we report a metabolism-independent function of NADPH in modulating epigenetic status and transcription. We found that reduction of cellular NADPH levels by silencing malic enzyme (ME) or G6PD impairs global histone acetylation and transcription in both adipocytes and tumor cells. These effects can be reversed by supplementation of exogenous NADPH or inhibition of histone deacetylase 3 (HDAC3). Mechanistically, NADPH or inhibition of histone deacetylase 3 (HDAC3). Mechanistically,NADPH directly interacts with HDAC3 and interrupts the association between HDAC3 and its co-activator Ncor2 (SMRT) or Ncor1, thereby impairs HDAC3 activation. Interestingly, it appears that NADPH and Ins(1,4,5,6)P4 bind to the same domains on HDAC3, and NADPH has relatively higher affinity towards HDAC3. Thus, while Ins(1,4,5,6)P4 acts as an ‘intermolecular glue’, NADPH may function as a HDAC3-Ncor assembly inhibitor. Collectively, our findings uncovered a previous unidentified and metabolism-independent role of NADPH in controlling epigenetic change and gene expression by acting as an endogenous inhibitor of HDAC3.
2020-11-27 | GSE137694 | GEO