Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Xylose fermentation performance was studied of a previously developed Saccharomyces cerevisiae strain TMB 3057, carrying high xylose reductase (XR) and xylitol dehydrogenase (XDH) activity, overexpressed non-oxidative pentose phosphate pathway (PPP) and deletion of the aldose reductase gene GRE3. The fermentation performance of TMB 3057 was significantly improved by increased ethanol production and reduced xylitol formation compared with the reference strain TMB 3001. The effects of the individual genetic modifications on xylose fermentation were investigated by comparing five isogenic strains with single or combined modifications. All strains with high activity of both XR and XDH had increased ethanol yields and significantly decreased xylitol yields. The presence of glucose further reduced xylitol formation in all studied strains. High activity of the non-oxidative PPP improved the xylose consumption rate. The results indicate that ethanolic xylose fermentation by recombinant S. cerevisiae expressing XR and XDH is governed by the efficiency by which xylose is introduced in the central metabolism.
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PMID:High activity of xylose reductase and xylitol dehydrogenase improves xylose fermentation by recombinant Saccharomyces cerevisiae. 1697 66

Vitamin C, a reducing agent and antioxidant, is a cofactor in reactions catalyzed by Cu(+)-dependent monooxygenases and Fe(2+)-dependent dioxygenases. It is synthesized, in vertebrates having this capacity, from d-glucuronate. The latter is formed through direct hydrolysis of uridine diphosphate (UDP)-glucuronate by enzyme(s) bound to the endoplasmic reticulum membrane, sharing many properties with, and most likely identical to, UDP-glucuronosyltransferases. Non-glucuronidable xenobiotics (aminopyrine, metyrapone, chloretone and others) stimulate the enzymatic hydrolysis of UDP-glucuronate, accounting for their effect to increase vitamin C formation in vivo. Glucuronate is converted to l-gulonate by aldehyde reductase, an enzyme of the aldo-keto reductase superfamily. l-Gulonate is converted to l-gulonolactone by a lactonase identified as SMP30 or regucalcin, whose absence in mice leads to vitamin C deficiency. The last step in the pathway of vitamin C synthesis is the oxidation of l-gulonolactone to l-ascorbic acid by l-gulonolactone oxidase, an enzyme associated with the endoplasmic reticulum membrane and deficient in man, guinea pig and other species due to mutations in its gene. Another fate of glucuronate is its conversion to d-xylulose in a five-step pathway, the pentose pathway, involving identified oxidoreductases and an unknown decarboxylase. Semidehydroascorbate, a major oxidation product of vitamin C, is reconverted to ascorbate in the cytosol by cytochrome b(5) reductase and thioredoxin reductase in reactions involving NADH and NADPH, respectively. Transmembrane electron transfer systems using ascorbate or NADH as electron donors serve to reduce semidehydroascorbate present in neuroendocrine secretory vesicles and in the extracellular medium. Dehydroascorbate, the fully oxidized form of vitamin C, is reduced spontaneously by glutathione, as well as enzymatically in reactions using glutathione or NADPH. The degradation of vitamin C in mammals is initiated by the hydrolysis of dehydroascorbate to 2,3-diketo-l-gulonate, which is spontaneously degraded to oxalate, CO(2) and l-erythrulose. This is at variance with bacteria such as Escherichia coli, which have enzymatic degradation pathways for ascorbate and probably also dehydroascorbate.
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PMID:Vitamin C. Biosynthesis, recycling and degradation in mammals. 1722 74

Cortisone or (in rodents) 11-dehydrocorticosterone are reduced to cortisol or corticosterone, respectively, by the oxo-reductase activity of 11beta-hydroxysteroid dehydrogenase type 1 (11-HSD1). This requires NADPH, generated by hexose-6-phosphate dehydrogenase (H6PD), a component of the pentose phosphate pathway. H6PD is located along with 11-HSD1 in the lumen of the endoplasmic reticulum (ER). Increasing or decreasing expression levels of H6PD in cultured cells has corresponding effects on the reductase activity of 11-HSD1. Mice carrying a targeted mutation in H6PD have drastically decreased 11-HSD1 oxo-reductase activity, but their 11-dehydrogenase activity is increased. They have many phenotypic features in common with mice carrying a mutation of 11-HSD1 itself. Polymorphisms in both H6PD and 11-HSD1 were originally identified in patients with apparent cortisone reductase deficiency (who have signs of hyperandrogenism and decreased urinary excretion of cortisol versus cortisone metabolites). However, these polymorphisms do not have detectable biochemical or physiologic effects when prospectively ascertained.
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PMID:Hexose 6-phosphate dehydrogenase (H6PD) and corticosteroid metabolism. 1724 46

An l-xylulose reductase identified from the genome sequence of the filamentous fungus Neurospora crassa was heterologously expressed in Escherichia coli as a His(6) tag fusion protein, purified, and characterized. The enzyme may be used in the production of xylitol from the major pentose components of hemicellulosic waste, d-xylose and l-arabinose.
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PMID:Biochemical characterization of an L-Xylulose reductase from Neurospora crassa. 1726 18

Production of bioethanol from forest and agricultural products requires a fermenting organism that converts all types of sugars in the raw material to ethanol in high yield and with a high rate. This review summarizes recent research aiming at developing industrial strains of Saccharomyces cerevisiae with the ability to ferment all lignocellulose-derived sugars. The properties required from the industrial yeast strains are discussed in relation to four benchmarks: (1) process water economy, (2) inhibitor tolerance, (3) ethanol yield, and (4) specific ethanol productivity. Of particular importance is the tolerance of the fermenting organism to fermentation inhibitors formed during fractionation/pretreatment and hydrolysis of the raw material, which necessitates the use of robust industrial strain background. While numerous metabolic engineering strategies have been developed in laboratory yeast strains, only a few approaches have been realized in industrial strains. The fermentation performance of the existing industrial pentose-fermenting S. cerevisiae strains in lignocellulose hydrolysate is reviewed. Ethanol yields of more than 0.4 g ethanol/g sugar have been achieved with several xylose-fermenting industrial strains such as TMB 3400, TMB 3006, and 424A(LNF-ST), carrying the heterologous xylose utilization pathway consisting of xylose reductase and xylitol dehydrogenase, which demonstrates the potential of pentose fermentation in improving lignocellulosic ethanol production.
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PMID:Towards industrial pentose-fermenting yeast strains. 1729 86

Metabolic engineering of Saccharomyces cerevisiae for ethanol production from D-xylose, an abundant sugar in plant biomass hydrolysates, has been pursued vigorously for the past 15 years. Whereas wild-type S. cerevisiae cannot ferment D-xylose, the keto-isomer D-xylulose can be metabolised slowly. Conversion of D-xylose into D-xylulose is therefore crucial in metabolic engineering of xylose fermentation by S. cerevisiae. Expression of heterologous xylose reductase and xylitol dehydrogenase does enable D-xylose utilisation, but intrinsic redox constraints of this pathway result in undesirable byproduct formation in the absence of oxygen. In contrast, expression of xylose isomerase (XI, EC 5.3.1.5), which directly interconverts D-xylose and D-xylulose, does not have these constraints. However, several problems with the functional expression of various bacterial and Archaeal XI genes have precluded successful use of XI in yeast metabolic engineering. This changed with the discovery of a fungal XI gene in Piromyces sp. E2, expression of which led to high XI activities in S. cerevisiae. When combined with over-expression of the genes of the non-oxidative pentose phosphate pathway of S. cerevisiae, the resulting strain grew anaerobically on D-xylose with a doubling time of ca. 8 h, with the same ethanol yield as on glucose. Additional evolutionary engineering was used to improve the fermentation kinetics of mixed-substrate utilisation, resulting in efficient D-xylose utilisation in synthetic media. Although industrial pilot experiments have already demonstrated high ethanol yields from the D-xylose present in plant biomass hydrolysates, strain robustness, especially with respect to tolerance to inhibitors present in hydrolysates, can still be further improved.
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PMID:Development of efficient xylose fermentation in Saccharomyces cerevisiae: xylose isomerase as a key component. 1784 24

The Hypocrea jecorina D-xylose reductase encoding gene xyl1 shows low basal transcript levels, and is induced by D-xylose, L-arabinose and L-arabinitol and, to a lesser extent, by lactose, D-galactose, galactitol and xylitol. The recombinantly expressed XYL1 catalyzes the NADPH-dependent reduction of the pentoses D-xylose and L-arabinose and the hexose D-galactose. Deletion of xyl1 slightly reduces growth on all carbon sources, but a significant decrease is found on D-xylose, L-arabinose and D-galactose. Similar to pentose degradation, XYL1 reduces D-galactose to galactitol in a recently identified second D-galactose pathway. Strains impaired in both D-galactose pathways are almost unable to grow on D-galactose. Deltaxyl1 strains show reduced growth on lactose and are impaired in beta-galactosidase expression and induction of the major cellobiohydrolase gene cbh1. A strain deleted in the cellulase regulator XYR1 is even more severely impaired in growth and beta-galactosidase expression on lactose, and does not produce any cbh1 transcript at all. In this strain, only a low basal level of xyl1 transcription is found on lactose. Galactitol, but not D-galactose is able to induce xyl1 transcription in a XYR1-independent manner. Our results show that the role of the H. jecorina XYL1 is not restricted to D-xylose catabolism and demonstrates its importance for induction of cellulases and beta-galactosidases.
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PMID:The D-xylose reductase of Hypocrea jecorina is the major aldose reductase in pentose and D-galactose catabolism and necessary for beta-galactosidase and cellulase induction by lactose. 1792 46

Candida arabinofermentans PYCC 5603(T) and Pichia guilliermondii PYCC 3012 were shown to grow well on L-arabinose, albeit exhibiting distinct features that justify an in-depth comparative study of their respective pentose catabolism. Carbon-13 labeling experiments coupled with in vivo nuclear magnetic resonance (NMR) spectroscopy were used to investigate L-arabinose metabolism in these yeasts, thereby complementing recently reported physiological and enzymatic data. The label supplied in L-[2-(13)C]arabinose to nongrowing cells, under aerobic conditions, was found on C-1 and C-2 of arabitol and ribitol, on C-2 of xylitol, and on C-1, C-2, and C-3 of trehalose. The detection of labeled arabitol and xylitol constitutes additional evidence for the operation in yeast of the redox catabolic pathway, which is widespread among filamentous fungi. Furthermore, labeling at position C-1 of trehalose and arabitol demonstrates that glucose-6-phosphate is recycled through the oxidative pentose phosphate pathway (PPP). This result was interpreted as a metabolic strategy to regenerate NADPH, the cofactor essential for sustaining l-arabinose catabolism at the level of L-arabinose reductase and L-xylulose reductase. Moreover, the observed synthesis of D-arabitol and ribitol provides a route with which to supply NAD(+) under oxygen-limiting conditions. In P. guilliermondii PYCC 3012, the strong accumulation of L-arabitol (intracellular concentration of up to 0.4 M) during aerobic L-arabinose metabolism indicates the existence of a bottleneck at the level of L-arabitol 4-dehydrogenase. This report provides the first experimental evidence for a link between L-arabinose metabolism in fungi and the oxidative branch of the PPP and suggests rational guidelines for the design of strategies for the production of new and efficient L-arabinose-fermenting yeasts.
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PMID:Use of in vivo 13C nuclear magnetic resonance spectroscopy to elucidate L-arabinose metabolism in yeasts. 1824 53

The effects of oxygen limitation on xylose fermentation of Neurospora crassa AS3.1602 were studied using batch cultures. The maximum yield of ethanol was 0.34 g/g at oxygen transfer rate (OTR) of 8.4 mmol/L.h. The maximum yield of xylitol was 0.33 g/g at OTR of 5.1 mmol/L.h. Oxygen limitation greatly affected mycelia growth and xylitol and ethanol productions. The specific growth rate (micro) decreased 82% from 0.045 to 0.008 h(-1) when OTR changed from 12.6 to 8.4 mmol/L.h. Intracellular metabolites of the pentose phosphate pathway, glycolysis, and tricarboxylic acid cycle were determined at various OTRs. Concentrations of most intracellular metabolites decreased with the increase in oxygen limitation. Intracellular enzyme activities of xylose reductase, xylitol dehydrogenase, and xylulokinase, the first three enzymes in xylose metabolic pathway, decreased with the increase in oxygen limitation, resulting in the decreased xylose uptake rate. Under all tested conditions, transaldolase and transketolase activities always maintained at low levels, indicating a great control on xylose metabolism. The enzyme of glucose-6-phosphate dehydrogenase played a major role in NADPH regeneration, and its activity decreased remarkably with the increase in oxygen limitation.
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PMID:Effects of oxygen limitation on xylose fermentation, intracellular metabolites, and key enzymes of Neurospora crassa AS3.1602. 1842 10

Proline metabolism in mammals involves two other amino acids, glutamate and ornithine, and five enzymatic activities, Delta(1)-pyrroline-5-carboxylate (P5C) reductase (P5CR), proline oxidase, P5C dehydrogenase, P5C synthase and ornithine-delta-aminotransferase (OAT). With the exception of OAT, which catalyzes a reversible reaction, the other four enzymes are unidirectional, suggesting that proline metabolism is purpose-driven, tightly regulated, and compartmentalized. In addition, this tri-amino-acid system also links with three other pivotal metabolic systems, namely the TCA cycle, urea cycle, and pentose phosphate pathway. Abnormalities in proline metabolism are relevant in several diseases: six monogenic inborn errors involving metabolism and/or transport of proline and its immediate metabolites have been described. Recent advances in the Human Genome Project, in silico database mining techniques, and research in dissecting the molecular basis of proline metabolism prompted us to utilize functional genomic approaches to analyze human genes which encode proline metabolic enzymes in the context of gene structure, regulation of gene expression, mRNA variants, protein isoforms, and single nucleotide polymorphisms.
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PMID:Functional genomics and SNP analysis of human genes encoding proline metabolic enzymes. 1850 9


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