Zeitschriftenartikel: „Glyoxylate shunt“

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Long, Bui Hoang Dang, Masahiro Nishiyama, Rintaro Sato, Tomonari Tanaka, Hitomi Ohara und Yuji Aso. „Production of Glyoxylate from Glucose in Engineered Escherichia coli“. Fermentation 9, Nr. 6 (31.05.2023): 534. http://dx.doi.org/10.3390/fermentation9060534.

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Glyoxylates are essential intermediates in several metabolic pathways and have a broad range of industrial applications. In this study, we propose a novel method for producing glyoxylate from glucose using engineered Escherichia coli BW25113. To direct the production of glyoxylate from glucose, malate synthase A (aceB), malate synthase G (glcB), glyoxylate carboligase (gcl), and glyoxylate/hydroxypyruvate reductase A (ycdW) genes were disrupted, and the glyoxylate shunt was reinforced in the disruptants by the overexpression of citrate synthase (gltA) and isocitrate lyase (aceA). In flask cultivation using M9 medium supplemented with 1% glucose, the disruptant E. coli BW25113 ΔaceB ΔglcB Δgcl ΔycdW produced 0.93 ± 0.17 g/L of glyoxylate. Further overexpression of gltA and aceA in the disruptant resulted in an improvement in glyoxylate production to 1.15 ± 0.02 g/L. By expressing a heterologous gene, pyc, in the engineered E. coli, the accumulation of intracellular oxaloacetate remarkably improved, leading to glyoxylate production of up to 2.42 ± 0.00 g/L with specific productivity at 4.22 ± 0.09 g/g-cell. To date, this is the highest reported titer and specific productivity of glyoxylate in E. coli.

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Dolan, Stephen K., und Martin Welch. „The Glyoxylate Shunt, 60 Years On“. Annual Review of Microbiology 72, Nr. 1 (08.09.2018): 309–30. http://dx.doi.org/10.1146/annurev-micro-090817-062257.

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2017 marks the 60th anniversary of Krebs’ seminal paper on the glyoxylate shunt (and coincidentally, also the 80th anniversary of his discovery of the citric acid cycle). Sixty years on, we have witnessed substantial developments in our understanding of how flux is partitioned between the glyoxylate shunt and the oxidative decarboxylation steps of the citric acid cycle. The last decade has shown us that the beautifully elegant textbook mechanism that regulates carbon flux through the shunt in E. coli is an oversimplification of the situation in many other bacteria. The aim of this review is to assess how this new knowledge is impacting our understanding of flux control at the TCA cycle/glyoxylate shunt branch point in a wider range of genera, and to summarize recent findings implicating a role for the glyoxylate shunt in cellular functions other than metabolism.

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Puckett, Susan, Carolina Trujillo, Zhe Wang, Hyungjin Eoh, Thomas R. Ioerger, Inna Krieger, James Sacchettini, Dirk Schnappinger, Kyu Y. Rhee und Sabine Ehrt. „Glyoxylate detoxification is an essential function of malate synthase required for carbon assimilation inMycobacterium tuberculosis“. Proceedings of the National Academy of Sciences 114, Nr. 11 (06.03.2017): E2225—E2232. http://dx.doi.org/10.1073/pnas.1617655114.

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The glyoxylate shunt is a metabolic pathway of bacteria, fungi, and plants used to assimilate even-chain fatty acids (FAs) and has been implicated in persistence ofMycobacterium tuberculosis(Mtb). Recent work, however, showed that the first enzyme of the glyoxylate shunt, isocitrate lyase (ICL), may mediate survival ofMtbduring the acute and chronic phases of infection in mice through physiologic functions apart from fatty acid metabolism. Here, we report that malate synthase (MS), the second enzyme of the glyoxylate shunt, is essential for in vitro growth and survival ofMtbon even-chain fatty acids, in part, for a previously unrecognized activity: mitigating the toxicity of glyoxylate excess arising from metabolism of even-chain fatty acids. Metabolomic profiling revealed that MS-deficientMtbcultured on fatty acids accumulated high levels of the ICL aldehyde endproduct, glyoxylate, and increased levels of acetyl phosphate, acetoacetyl coenzyme A (acetoacetyl-CoA), butyryl CoA, acetoacetate, and β-hydroxybutyrate. These changes were indicative of a glyoxylate-induced state of oxaloacetate deficiency, acetate overload, and ketoacidosis. Reduction of intrabacterial glyoxylate levels using a chemical inhibitor of ICL restored growth of MS-deficientMtb, despite inhibiting entry of carbon into the glyoxylate shunt. In vivo depletion of MS resulted in sterilization ofMtbin both the acute and chronic phases of mouse infection. This work thus identifies glyoxylate detoxification as an essential physiologic function ofMtbmalate synthase and advances its validation as a target for drug development.

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Schink, Bernhard. „An alternative to the glyoxylate shunt“. Molecular Microbiology 73, Nr. 6 (September 2009): 975–77. http://dx.doi.org/10.1111/j.1365-2958.2009.06835.x.

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5

Ahn, Sungeun, Jaejoon Jung, In-Ae Jang, Eugene L. Madsen und Woojun Park. „Role of Glyoxylate Shunt in Oxidative Stress Response“. Journal of Biological Chemistry 291, Nr. 22 (01.04.2016): 11928–38. http://dx.doi.org/10.1074/jbc.m115.708149.

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McVey, Alyssa C., Sean Bartlett, Mahmud Kajbaf, Annalisa Pellacani, Viviana Gatta, Päivi Tammela, David R. Spring und Martin Welch. „2-Aminopyridine Analogs Inhibit Both Enzymes of the Glyoxylate Shunt in Pseudomonas aeruginosa“. International Journal of Molecular Sciences 21, Nr. 7 (03.04.2020): 2490. http://dx.doi.org/10.3390/ijms21072490.

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Pseudomonas aeruginosa is an opportunistic pathogen responsible for many hospital-acquired infections. P. aeruginosa can thrive in diverse infection scenarios by rewiring its central metabolism. An example of this is the production of biomass from C2 nutrient sources such as acetate via the glyoxylate shunt when glucose is not available. The glyoxylate shunt is comprised of two enzymes, isocitrate lyase (ICL) and malate synthase G (MS), and flux through the shunt is essential for the survival of the organism in mammalian systems. In this study, we characterized the mode of action and cytotoxicity of structural analogs of 2-aminopyridines, which have been identified by earlier work as being inhibitory to both shunt enzymes. Two of these analogs were able to inhibit ICL and MS in vitro and prevented growth of P. aeruginosa on acetate (indicating cell permeability). Moreover, the compounds exerted negligible cytotoxicity against three human cell lines and showed promising in vitro drug metabolism and safety profiles. Isothermal titration calorimetry was used to confirm binding of one of the analogs to ICL and MS, and the mode of enzyme inhibition was determined. Our data suggest that these 2-aminopyridine analogs have potential as anti-pseudomonal agents.

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Ritson, Dougal J. „A cyanosulfidic origin of the Krebs cycle“. Science Advances 7, Nr. 33 (August 2021): eabh3981. http://dx.doi.org/10.1126/sciadv.abh3981.

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The centrality of the Krebs cycle in metabolism has long been interpreted as evidence of its antiquity, and consequently, questions regarding its provenance, and whether it initially functioned as a cycle or not, have received much attention. The present report shows that prebiotic oxidation of α-hydroxy carboxylates can be achieved by UV photolysis of a simple geochemical species (HS−), which leads to α-oxo carboxylates that feature in the Krebs cycle and glyoxylate shunt. Further reaction of these products leads to almost all intermediates of the Krebs cycle proper, succinate semialdehyde bypass, and glyoxylate shunt. Fumarate, the missing Krebs cycle component, and the required α-hydroxy carboxylates can be provided by a highly related hydrogen cyanide chemistry, which also provides precursors for amino acids, nucleotides, and phospholipids.

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Nanchen, Annik, Alexander Schicker und Uwe Sauer. „Nonlinear Dependency of Intracellular Fluxes on Growth Rate in Miniaturized Continuous Cultures of Escherichia coli“. Applied and Environmental Microbiology 72, Nr. 2 (Februar 2006): 1164–72. http://dx.doi.org/10.1128/aem.72.2.1164-1172.2006.

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ABSTRACT A novel mini-scale chemostat system was developed for the physiological characterization of 10-ml cultures. The parallel operation of eight such mini-scale chemostats was exploited for systematic 13C analysis of intracellular fluxes over a broad range of growth rates in glucose-limited Escherichia coli. As expected, physiological variables changed monotonously with the dilution rate, allowing for the assessment of maintenance metabolism. Despite the linear dependence of total cellular carbon influx on dilution rate, the distribution of almost all major fluxes varied nonlinearly with dilution rate. Most prominent were the distinct maximum of glyoxylate shunt activity and the concomitant minimum of tricarboxylic acid cycle activity at low to intermediate dilution rates of 0.05 to 0.2 h−1. During growth on glucose, this glyoxylate shunt activity is best understood from a network perspective as the recently described phosphoenolpyruvate (PEP)-glyoxylate cycle that oxidizes PEP (or pyruvate) to CO2. At higher or extremely low dilution rates, in vivo PEP-glyoxylate cycle activity was low or absent. The step increase in pentose phosphate pathway activity at around 0.2 h−1 was not related to the cellular demand for the reduction equivalent NADPH, since NADPH formation was 20 to 50% in excess of the anabolic demand at all dilution rates. The results demonstrate that mini-scale continuous cultivation enables quantitative and parallel characterization of intra- and extracellular phenotypes in steady state, thereby greatly reducing workload and costs for stable-isotope experiments.

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Davis, W. L., R. G. Jones und D. B. Goodman. „Cytochemical localization of malate synthase in amphibian fat body adipocytes: possible glyoxylate cycle in a vertebrate.“ Journal of Histochemistry & Cytochemistry 34, Nr. 5 (Mai 1986): 689–92. http://dx.doi.org/10.1177/34.5.3701032.

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The adipocytes of amphibian abdominal fat bodies contain typical microperoxisomes, as indicated by their fine structure. Electron microscopic cytochemistry showed that these organelles contain the enzymes catalase, typical for peroxisomes, and malate synthase. The latter is an enzymatic component characteristic of the glyoxylate cycle, a biochemical pathway known to exist in plant glyoxysomes (peroxisomes). This metabolic pathway makes possible the net conversion of lipid to carbohydrate. Toad adipocytes may represent yet another example of vertebrate peroxisomes which contain one of the marker enzymes (malate synthase) characteristic of the glyoxylate shunt.

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Sarao, Renu, Howard D. McCurdy und Luciano Passador. „Enzymes of the intermediary carbohydrate metabolism of Polyangium cellulosum“. Canadian Journal of Microbiology 31, Nr. 12 (01.12.1985): 1142–46. http://dx.doi.org/10.1139/m85-215.

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Crude extracts of vegetative cells of the cellulolytic myxobacter Polyangium cellulosum contained significant levels of the enzymes of the tricarboxylic acid cycle and the glyoxylate cycle. Key enzymes of glycolysis and the pentose phosphate shunt were also detected. Specific activities of hexokinase and fructose- 1,6-diphosphate aldolase exhibited a 10-fold increase when the cells were grown in complex medium containing glucose. Cytochromes of a, b, and c type were demonstrated. By the use of a dispersly growing strain of P. cellulosum, its generation time was determined to be 22–24 h. This study suggests that the organism probably uses glycolysis and citric acid cycle for complete oxidation of glucose. The exact role of the glyoxylate cycle and pentose phosphate shunt cannot be deduced from this study. This is the first report on the study of intermediary carbohydrate metabolism in any member of the family Polyangiaceae.

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Wilson, R. B., und S. R. Maloy. „Isolation and characterization of Salmonella typhimurium glyoxylate shunt mutants.“ Journal of Bacteriology 169, Nr. 7 (1987): 3029–34. http://dx.doi.org/10.1128/jb.169.7.3029-3034.1987.

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Fang, Ferric C., Stephen J. Libby, Margaret E. Castor und Angela M. Fung. „Isocitrate Lyase (AceA) Is Required for Salmonella Persistence but Not for Acute Lethal Infection in Mice“. Infection and Immunity 73, Nr. 4 (April 2005): 2547–49. http://dx.doi.org/10.1128/iai.73.4.2547-2549.2005.

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ABSTRACT Isocitrate lyase is required for fatty acid utilization via the glyoxylate shunt. Although isocitrate lyase is essential for Salmonella persistence during chronic infection, it is dispensable for acute lethal infection in mice. Substrate availability in the phagosome appears to evolve over time, with increasing fatty acid dependence during chronic infection.

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Ogawa, Tadashi, Keiko Murakami, Hirotada Mori, Nobuyoshi Ishii, Masaru Tomita und Masataka Yoshin. „Role of Phosphoenolpyruvate in the NADP-Isocitrate Dehydrogenase and Isocitrate Lyase Reaction in Escherichia coli“. Journal of Bacteriology 189, Nr. 3 (01.12.2006): 1176–78. http://dx.doi.org/10.1128/jb.01628-06.

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ABSTRACT Phosphoenolpyruvate inhibited Escherichia coli NADP-isocitrate dehydrogenase allosterically (Ki of 0.31 mM) and isocitrate lyase uncompetitively (Ki ′ of 0.893 mM). Phosphoenolpyruvate enhances the uncompetitive inhibition of isocitrate lyase by increasing isocitrate, which protects isocitrate dehydrogenase from the inhibition, and contributes to the control through the tricarboxylic acid cycle and glyoxylate shunt.

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Lee, Ji, Sanghak Cha, Chae Kang, Geon Lee, Hyun Lim und Gyoo Jung. „Efficient Conversion of Acetate to 3-Hydroxypropionic Acid by Engineered Escherichia coli“. Catalysts 8, Nr. 11 (07.11.2018): 525. http://dx.doi.org/10.3390/catal8110525.

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Acetate, which is an abundant carbon source, is a potential feedstock for microbial processes that produce diverse value-added chemicals. In this study, we produced 3-hydroxypropionic acid (3-HP) from acetate with engineered Escherichia coli. For the efficient conversion of acetate to 3-HP, we initially introduced heterologous mcr (encoding malonyl-CoA reductase) from Chloroflexus aurantiacus. Then, the acetate assimilating pathway and glyoxylate shunt pathway were activated by overexpressing acs (encoding acetyl-CoA synthetase) and deleting iclR (encoding the glyoxylate shunt pathway repressor). Because a key precursor malonyl-CoA is also consumed for fatty acid synthesis, we decreased carbon flux to fatty acid synthesis by adding cerulenin. Subsequently, we found that inhibiting fatty acid synthesis dramatically improved 3-HP production (3.00 g/L of 3-HP from 8.98 g/L of acetate). The results indicated that acetate can be used as a promising carbon source for microbial processes and that 3-HP can be produced from acetate with a high yield (44.6% of the theoretical maximum yield).

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Ha, Sunhee, Bora Shin und Woojun Park. „Lack of glyoxylate shunt dysregulates iron homeostasis in Pseudomonas aeruginosa“. Microbiology 164, Nr. 4 (01.04.2018): 587–99. http://dx.doi.org/10.1099/mic.0.000623.

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Kumari, Suman, Christine M. Beatty, Douglas F. Browning, Stephen J. W. Busby, Erica J. Simel, Galadriel Hovel-Miner und Alan J. Wolfe. „Regulation of Acetyl Coenzyme A Synthetase inEscherichia coli“. Journal of Bacteriology 182, Nr. 15 (01.08.2000): 4173–79. http://dx.doi.org/10.1128/jb.182.15.4173-4179.2000.

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ABSTRACT Cells of Escherichia coli growing on sugars that result in catabolite repression or amino acids that feed into glycolysis undergo a metabolic switch associated with the production and utilization of acetate. As they divide exponentially, these cells excrete acetate via the phosphotransacetylase-acetate kinase pathway. As they begin the transition to stationary phase, they instead resorb acetate, activate it to acetyl coenzyme A (acetyl-CoA) by means of the enzyme acetyl-CoA synthetase (Acs) and utilize it to generate energy and biosynthetic components via the tricarboxylic acid cycle and the glyoxylate shunt, respectively. Here, we present evidence that this switch occurs primarily through the induction of acs and that the timing and magnitude of this induction depend, in part, on the direct action of the carbon regulator cyclic AMP receptor protein (CRP) and the oxygen regulator FNR. It also depends, probably indirectly, upon the glyoxylate shunt repressor IclR, its activator FadR, and many enzymes involved in acetate metabolism. On the basis of these results, we propose that cells induce acs, and thus their ability to assimilate acetate, in response to rising cyclic AMP levels, falling oxygen partial pressure, and the flux of carbon through acetate-associated pathways.

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Bianco, C., E. Imperlini, R. Calogero, B. Senatore, P. Pucci und R. Defez. „Indole-3-acetic acid regulates the central metabolic pathways in Escherichia coli“. Microbiology 152, Nr. 8 (01.08.2006): 2421–31. http://dx.doi.org/10.1099/mic.0.28765-0.

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The physiological changes induced by indoleacetic acid (IAA) treatment were investigated in the totally sequenced Escherichia coli K-12 MG1655. DNA macroarrays were used to measure the mRNA levels for all the 4290 E. coli protein-coding genes; 50 genes (1.1 %) exhibited significantly different expression profiles. In particular, genes involved in the tricarboxylic acid cycle, the glyoxylate shunt and amino acid biosynthesis (leucine, isoleucine, valine and proline) were up-regulated, whereas the fermentative adhE gene was down-regulated. To confirm the indications obtained from the macroarray analysis the activity of 34 enzymes involved in central metabolism was measured; this showed an activation of the tricarboxylic acid cycle and the glyoxylate shunt. The malic enzyme, involved in the production of pyruvate, and pyruvate dehydrogenase, required for the channelling of pyruvate into acetyl-CoA, were also induced in IAA-treated cells. Moreover, it was shown that the enhanced production of acetyl-CoA and the decrease of NADH/NAD+ ratio are connected with the molecular process of the IAA response. The results demonstrate that IAA treatment is a stimulus capable of inducing changes in gene expression, enzyme activity and metabolite level involved in central metabolic pathways in E. coli.

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Jiang, Min, Shu-wen Liu, Jiang-feng Ma, Ke-quan Chen, Li Yu, Fang-fang Yue, Bing Xu und Ping Wei. „Effect of Growth Phase Feeding Strategies on Succinate Production by Metabolically Engineered Escherichia coli“. Applied and Environmental Microbiology 76, Nr. 4 (28.12.2009): 1298–300. http://dx.doi.org/10.1128/aem.02190-09.

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ABSTRACT Aerobic growth conditions significantly influenced anaerobic succinate production in two-stage fermentation by Escherichia coli AFP111 with knockouts in rpoS, pflAB, ldhA, and ptsG genes. At a low cell growth rate limited by glucose, enzymes involved in the reductive arm of the tricarboxylic acid cycle and the glyoxylate shunt showed elevated activities, providing AFP111 with intracellular redox balance and increased succinic acid yield and productivity.

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Dean, Jason T., Linh Tran, Simon Beaven, Peter Tontonoz, Karen Reue, Katrina M. Dipple und James C. Liao. „Resistance to Diet-Induced Obesity in Mice with Synthetic Glyoxylate Shunt“. Cell Metabolism 9, Nr. 6 (Juni 2009): 525–36. http://dx.doi.org/10.1016/j.cmet.2009.04.008.

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Regev-Rudzki, Neta, Sharon Karniely, Nitzan Natani Ben-Haim und Ophry Pines. „Yeast Aconitase in Two Locations and Two Metabolic Pathways: Seeing Small Amounts Is Believing“. Molecular Biology of the Cell 16, Nr. 9 (September 2005): 4163–71. http://dx.doi.org/10.1091/mbc.e04-11-1028.

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The distribution of identical enzymatic activities between different subcellular compartments is a fundamental process of living cells. At present, the Saccharomyces cerevisiae aconitase enzyme has been detected only in mitochondria, where it functions in the tricarboxylic acid (TCA) cycle and is considered a mitochondrial matrix marker. We developed two strategies for physical and functional detection of aconitase in the yeast cytosol: 1) we fused the α peptide of the β-galactosidase enzyme to aconitase and observed α complementation in the cytosol; and 2) we created an ACO1-URA3 hybrid gene, which allowed isolation of strains in which the hybrid protein is exclusively targeted to mitochondria. These strains display a specific phenotype consistent with glyoxylate shunt elimination. Together, our data indicate that yeast aconitase isoenzymes distribute between two distinct subcellular compartments and participate in two separate metabolic pathways; the glyoxylate shunt in the cytosol and the TCA cycle in mitochondria. We maintain that such dual distribution phenomena have a wider occurrence than recorded currently, the reason being that in certain cases there is a small fraction of one of the isoenzymes, in one of the locations, making its detection very difficult. We term this phenomenon of highly uneven isoenzyme distribution “eclipsed distribution.”

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Crousilles, Audrey, Stephen K. Dolan, Paul Brear, Dimitri Y. Chirgadze und Martin Welch. „Gluconeogenic precursor availability regulates flux through the glyoxylate shunt in Pseudomonas aeruginosa“. Journal of Biological Chemistry 293, Nr. 37 (20.07.2018): 14260–69. http://dx.doi.org/10.1074/jbc.ra118.004514.

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Dean, Jason T., Matthew L. Rizk, Yikun Tan, Katrina M. Dipple und James C. Liao. „Ensemble Modeling of Hepatic Fatty Acid Metabolism with a Synthetic Glyoxylate Shunt“. Biophysical Journal 98, Nr. 8 (April 2010): 1385–95. http://dx.doi.org/10.1016/j.bpj.2009.12.4308.

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Miller, Rhea M., Andrew P. Tomaras, Adam P. Barker, Dennis R. Voelker, Edward D. Chan, Adriana I. Vasil und Michael L. Vasil. „Pseudomonas aeruginosa Twitching Motility-Mediated Chemotaxis towards Phospholipids and Fatty Acids: Specificity and Metabolic Requirements“. Journal of Bacteriology 190, Nr. 11 (04.04.2008): 4038–49. http://dx.doi.org/10.1128/jb.00129-08.

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ABSTRACT Pseudomonas aeruginosa demonstrates type IV pilus-mediated directional twitching motility up a gradient of phosphatidylethanolamine (PE). Only one of four extracellular phospholipases C of P. aeruginosa (i.e., PlcB), while not required for twitching motility per se, is required for twitching-mediated migration up a gradient of PE or phosphatidylcholine. Whether other lipid metabolism genes are associated with this behavior was assessed by analysis of transcription during twitching up a PE gradient in comparison to transcription during twitching in the absence of any externally applied phospholipid. Data support the hypothesis that PE is further degraded and that the long-chain fatty acid (LCFA) moieties of PE are completely metabolized via β-oxidation and the glyoxylate shunt. It was discovered that P. aeruginosa exhibits twitching-mediated chemotaxis toward unsaturated LCFAs (e.g., oleic acid), but not saturated LCFAs (e.g., stearic acid) of corresponding lengths. Analysis of mutants that are deficient in glyoxylate shunt enzymes, specifically isocitrate lyase (ΔaceA) and malate synthase (ΔaceB), suggested that the complete metabolism of LCFAs through this pathway was required for the migration of P. aeruginosa up a gradient of PE or unsaturated LCFAs. At this point, our data suggested that this process should be classified as energy taxis. However, further evaluation of the ability of the ΔaceA and ΔaceB mutants to migrate up a gradient of PE or unsaturated LCFAs in the presence of an alternative energy source clearly indicated that metabolism of LCFAs for energy is not required for chemotaxis toward these compounds.

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Donèche, Bernard. „Carbohydrate metabolism and gluconic acid synthesis by Botrytis cinerea“. Canadian Journal of Botany 67, Nr. 10 (01.10.1989): 2888–93. http://dx.doi.org/10.1139/b89-370.

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The pathways of glucose catabolism were examined in a B. cinerea strain isolated from grape. Respirometric and enzymatic studies indicated that this plant parasite catabolized glucose through the Embden–Meyerhof and hexose monophosphate shunt pathways. Data also suggested functioning of an active tricarboxylic acid cycle and presence of the glyoxylate cycle. Direct oxidation of glucose by means of glucose oxidase led to gluconic acid accumulation in the medium during the stationary phase of growth. Part of the glucose oxidase was extracellular and could have technological consequences in wine making.

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Regev-Rudzki, Neta, Emil Battat, Israel Goldberg und Ophry Pines. „Dual localization of fumarase is dependent on the integrity of the glyoxylate shunt“. Molecular Microbiology 72, Nr. 2 (April 2009): 297–306. http://dx.doi.org/10.1111/j.1365-2958.2009.06659.x.

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Yang, Jing, Wenwen Yang, Jun Feng, Jie Chen, Min Jiang und Xiang Zou. „Enhanced polymalic acid production from the glyoxylate shunt pathway under exogenous alcohol stress“. Journal of Biotechnology 275 (Juni 2018): 24–30. http://dx.doi.org/10.1016/j.jbiotec.2018.04.001.

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Klinke, Stefan, Michael Dauner, George Scott, Birgit Kessler und Bernard Witholt. „Inactivation of Isocitrate Lyase Leads to Increased Production of Medium-Chain-Length Poly(3-Hydroxyalkanoates) inPseudomonas putida“. Applied and Environmental Microbiology 66, Nr. 3 (01.03.2000): 909–13. http://dx.doi.org/10.1128/aem.66.3.909-913.2000.

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ABSTRACT Medium-chain-length (mcl) poly(3-hydroxyalkanoates) (PHAs) are storage polymers that are produced from various substrates and accumulate in Pseudomonas strains belonging to rRNA homology group I. In experiments aimed at increasing PHA production inPseudomonas strains, we generated an mcl PHA-overproducing mutant of Pseudomonas putida KT2442 by transposon mutagenesis, in which the aceA gene was knocked out. This mutation inactivated the glyoxylate shunt and reduced the in vitro activity of isocitrate dehydrogenase, a rate-limiting enzyme of the citric acid cycle. The genotype of the mutant was confirmed by DNA sequencing, and the phenotype was confirmed by biochemical experiments. The aceA mutant was not able to grow on acetate as a sole carbon source due to disruption of the glyoxylate bypass and exhibited two- to fivefold lower isocitrate dehydrogenase activity than the wild type. During growth on gluconate, the difference between the mean PHA accumulation in the mutant and the mean PHA accumulation in the wild-type strain was 52%, which resulted in a significant increase in the amount of mcl PHA at the end of the exponential phase in the mutantP. putida KT217. On the basis of a stoichiometric flux analysis we predicted that knockout of the glyoxylate pathway in addition to reduced flux through isocitrate dehydrogenase should lead to increased flux into the fatty acid synthesis pathway. Therefore, enhanced carbon flow towards the fatty acid synthesis pathway increased the amount of mcl PHA that could be accumulated by the mutant.

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Nanchen, Annik, Alexander Schicker, Olga Revelles und Uwe Sauer. „Cyclic AMP-Dependent Catabolite Repression Is the Dominant Control Mechanism of Metabolic Fluxes under Glucose Limitation in Escherichia coli“. Journal of Bacteriology 190, Nr. 7 (25.01.2008): 2323–30. http://dx.doi.org/10.1128/jb.01353-07.

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ABSTRACT Although a whole arsenal of mechanisms are potentially involved in metabolic regulation, it is largely uncertain when, under which conditions, and to which extent a particular mechanism actually controls network fluxes and thus cellular physiology. Based on 13C flux analysis of Escherichia coli mutants, we elucidated the relevance of global transcriptional regulation by ArcA, ArcB, Cra, CreB, CreC, Crp, Cya, Fnr, Hns, Mlc, OmpR, and UspA on aerobic glucose catabolism in glucose-limited chemostat cultures at a growth rate of 0.1 h−1. The by far most relevant control mechanism was cyclic AMP (cAMP)-dependent catabolite repression as the inducer of the phosphoenolpyruvate (PEP)-glyoxylate cycle and thus low tricarboxylic acid cycle fluxes. While all other mutants and the reference E. coli strain exhibited high glyoxylate shunt and PEP carboxykinase fluxes, and thus high PEP-glyoxylate cycle flux, this cycle was essentially abolished in both the Crp and Cya mutants, which lack the cAMP-cAMP receptor protein complex. Most other mutations were phenotypically silent, and only the Cra and Hns mutants exhibited slightly altered flux distributions through PEP carboxykinase and the tricarboxylic acid cycle, respectively. The Cra effect on PEP carboxykinase was probably the consequence of a specific control mechanism, while the Hns effect appears to be unspecific. For central metabolism, the available data thus suggest that a single transcriptional regulation process exerts the dominant control under a given condition and this control is highly specific for a single pathway or cycle within the network.

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Cai, Yuanfeng, Juanli Yun und Zhongjun Jia. „Phylogeny and Metabolic Potential of the Methanotrophic Lineage MO3 in Beijerinckiaceae from the Paddy Soil through Metagenome-Assembled Genome Reconstruction“. Microorganisms 10, Nr. 5 (01.05.2022): 955. http://dx.doi.org/10.3390/microorganisms10050955.

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Although the study of aerobic methane-oxidizing bacteria (MOB, methanotrophs) has been carried out for more than a hundred years, there are many uncultivated methanotrophic lineages whose metabolism is largely unknown. Here, we reconstructed a nearly complete genome of a Beijerinckiaceae methanotroph from the enrichment of paddy soil by using nitrogen-free M2 medium. The methanotroph labeled as MO3_YZ.1 had a size of 3.83 Mb, GC content of 65.6%, and 3442 gene-coding regions. Based on phylogeny of pmoA gene and genome and the genomic average nucleotide identity, we confirmed its affiliation to the MO3 lineage and a close relationship to Methylocapsa. MO3_YZ.1 contained mxaF- and xoxF-type methanol dehydrogenase. MO3_YZ.1 used the serine cycle to assimilate carbon and regenerated glyoxylate through the glyoxylate shunt as it contained isocitrate lyase and complete tricarboxylic acid cycle-coding genes. The ethylmalonyl-CoA pathway and Calvin–Benson–Bassham cycle were incomplete in MO3_YZ.1. Three acetate utilization enzyme-coding genes were identified, suggesting its potential ability to utilize acetate. The presence of genes for N2 fixation, sulfur transformation, and poly-β-hydroxybutyrate synthesis enable its survival in heterogeneous habitats with fluctuating supplies of carbon, nitrogen, and sulfur.

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Serafini, Agnese, Lendl Tan, Stuart Horswell, Steven Howell, Daniel J. Greenwood, Deborah M. Hunt, Minh‐Duy Phan et al. „Mycobacterium tuberculosis requires glyoxylate shunt and reverse methylcitrate cycle for lactate and pyruvate metabolism“. Molecular Microbiology 112, Nr. 4 (23.08.2019): 1284–307. http://dx.doi.org/10.1111/mmi.14362.

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Tang, Yinjie J., Judy S. Hwang, David E. Wemmer und Jay D. Keasling. „Shewanella oneidensis MR-1 Fluxome under Various Oxygen Conditions“. Applied and Environmental Microbiology 73, Nr. 3 (10.11.2006): 718–29. http://dx.doi.org/10.1128/aem.01532-06.

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ABSTRACT The central metabolic fluxes of Shewanella oneidensis MR-1 were examined under carbon-limited (aerobic) and oxygen-limited (microaerobic) chemostat conditions, using 13C-labeled lactate as the sole carbon source. The carbon labeling patterns of key amino acids in biomass were probed using both gas chromatography-mass spectrometry (GC-MS) and 13C nuclear magnetic resonance (NMR). Based on the genome annotation, a metabolic pathway model was constructed to quantify the central metabolic flux distributions. The model showed that the tricarboxylic acid (TCA) cycle is the major carbon metabolism route under both conditions. The Entner-Doudoroff and pentose phosphate pathways were utilized primarily for biomass synthesis (with a flux below 5% of the lactate uptake rate). The anaplerotic reactions (pyruvate to malate and oxaloacetate to phosphoenolpyruvate) and the glyoxylate shunt were active. Under carbon-limited conditions, a substantial amount (9% of the lactate uptake rate) of carbon entered the highly reversible serine metabolic pathway. Under microaerobic conditions, fluxes through the TCA cycle decreased and acetate production increased compared to what was found for carbon-limited conditions, and the flux from glyoxylate to glycine (serine-glyoxylate aminotransferase) became measurable. Although the flux distributions under aerobic, microaerobic, and shake flask culture conditions were different, the relative flux ratios for some central metabolic reactions did not differ significantly (in particular, between the shake flask and aerobic-chemostat groups). Hence, the central metabolism of S. oneidensis appears to be robust to environmental changes. Our study also demonstrates the merit of coupling GC-MS with 13C NMR for metabolic flux analysis to reduce the use of 13C-labeled substrates and to obtain more-accurate flux values.

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Rude, Thomas H., Dena L. Toffaletti, Gary M. Cox und John R. Perfect. „Relationship of the Glyoxylate Pathway to the Pathogenesis of Cryptococcus neoformans“. Infection and Immunity 70, Nr. 10 (Oktober 2002): 5684–94. http://dx.doi.org/10.1128/iai.70.10.5684-5694.2002.

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ABSTRACT Functional genomics has become a major focus in the study of microbial pathogenesis. This study used a functional genomic tool, differential display reverse transcription-PCR, to identify a transcriptional profile of Cryptococcus neoformans cells as they produced meningitis in an immunosuppressed host. This serial global gene expression during infection allowed for the identification of up- and down-regulated genes during infection. During this profiling, a single gene for the enzyme isocitrate lyase (ICL1) was found to be up regulated at 1 week of infection in a rabbit meningitis model and during a time of maximum host cellular response. The finding suggested that this enzyme and the glyoxylate shunt pathway are important to this yeast's energy production during infection. However, site-directed icl1 mutants had no apparent virulence defect in two animal models and no growth defect within macrophages. These observations suggest that although the yeast responded to a certain environmental cue(s) by an increase in ICL1 expression during infection, this gene was not necessary for progression of a C. neoformans infection. Compounds that specifically target only ICL1 are unlikely to cripple C. neoformans growth in vivo.

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Yano, Takanori, Nobuyuki Yoshida, Fujio Yu, Miki Wakamatsu und Hiroshi Takagi. „The glyoxylate shunt is essential for CO2-requiring oligotrophic growth of Rhodococcus erythropolis N9T-4“. Applied Microbiology and Biotechnology 99, Nr. 13 (10.03.2015): 5627–37. http://dx.doi.org/10.1007/s00253-015-6500-x.

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McKinney, John D., Kerstin Höner zu Bentrup, Ernesto J. Muñoz-Elías, Andras Miczak, Bing Chen, Wai-Tsing Chan, Dana Swenson, James C. Sacchettini, William R. Jacobs und David G. Russell. „Persistence of Mycobacterium tuberculosis in macrophages and mice requires the glyoxylate shunt enzyme isocitrate lyase“. Nature 406, Nr. 6797 (August 2000): 735–38. http://dx.doi.org/10.1038/35021074.

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Vico, Susana Hidalgo, Daniel Prieto, Rebeca Alonso Monge, Elvira Román und Jesús Pla. „The Glyoxylate Cycle Is Involved in White-Opaque Switching in Candida albicans“. Journal of Fungi 7, Nr. 7 (24.06.2021): 502. http://dx.doi.org/10.3390/jof7070502.

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Candida albicans is a commensal yeast that inhabits the gastrointestinal tract of humans. The master regulator of the white-opaque transition WOR1 has been implicated in the adaptation to this commensal status. A proteomic analysis of cells overexpressing this transcription factor (WOR1OE) suggested an altered metabolism of carbon sources and a phenotypic analysis confirmed this alteration. The WOR1OE cells are deficient in using trehalose and xylose and are unable to use 2C sources, which is consistent with a reduction in the amount of Icl1, the isocitrate lyase enzyme. The icl1Δ/Δ mutants overexpressing WOR1 are deficient in the production of phloxine B positive cells, a main characteristic of opaque cells, a phenotype also observed in mating type hemizygous mtla1Δ icl1Δ/Δ cells, suggesting the involvement of Icl1 in the adaptation to the commensal state. In fact, icl1Δ/Δ cells have reduced fitness in mouse gastrointestinal tract as compared with essentially isogenic heterozygous ICL1/icl1Δ, but overproduction of WOR1 in an icl1Δ/Δ mutant does not restore fitness. These results implicate the glyoxylate shunt in the adaptation to commensalism of C. albicans by mechanisms that are partially independent of WOR1.

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Soria, Sandra, Ofelia E. Carreón-Rodríguez, Ramón de Anda, Noemí Flores, Adelfo Escalante und Francisco Bolívar. „Transcriptional and Metabolic Response of a Strain of Escherichia coli PTS− to a Perturbation of the Energetic Level by Modification of [ATP]/[ADP] Ratio“. BioTech 13, Nr. 2 (10.04.2024): 10. http://dx.doi.org/10.3390/biotech13020010.

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The intracellular [ATP]/[ADP] ratio is crucial for Escherichia coli’s cellular functions, impacting transport, phosphorylation, signaling, and stress responses. Overexpression of F1-ATPase genes in E. coli increases glucose consumption, lowers energy levels, and triggers transcriptional responses in central carbon metabolism genes, particularly glycolytic ones, enhancing carbon flux. In this contribution, we report the impact of the perturbation of the energetic level in a PTS− mutant of E. coli by modifying the [ATP]/[ADP] ratio by uncoupling the cytoplasmic activity of the F1 subunit of the ATP synthase. The disruption of [ATP]/[ADP] ratio in the evolved strain of E. coli PB12 (PTS−) was achieved by the expression of the atpAGD operon encoding the soluble portion of ATP synthase F1-ATPase (strain PB12AGD+). The analysis of the physiological and metabolic response of the PTS− strain to the ATP disruption was determined using RT–qPCR of 96 genes involved in glucose and acetate transport, glycolysis and gluconeogenesis, pentose phosphate pathway (PPP), TCA cycle and glyoxylate shunt, several anaplerotic, respiratory chain, and fermentative pathways genes, sigma factors, and global regulators. The apt mutant exhibited reduced growth despite increased glucose transport due to decreased energy levels. It heightened stress response capabilities under glucose-induced energetic starvation, suggesting that the carbon flux from glycolysis is distributed toward the pentose phosphate and the Entner–Duodoroff pathway with the concomitant. Increase acetate transport, production, and utilization in response to the reduction in the [ATP]/[ADP] ratio. Upregulation of several genes encoding the TCA cycle and the glyoxylate shunt as several respiratory genes indicates increased respiratory capabilities, coupled possibly with increased availability of electron donor compounds from the TCA cycle, as this mutant increased respiratory capability by 240% more than in the PB12. The reduction in the intracellular concentration of cAMP in the atp mutant resulted in a reduced number of upregulated genes compared to PB12, suggesting that the mutant remains a robust genetic background despite the severe disruption in its energetic level.

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Ascensao, Joao A., Pratik Datta, Baris Hancioglu, Eduardo Sontag, Maria L. Gennaro und Oleg A. Igoshin. „Non-monotonic Response to Monotonic Stimulus: Regulation of Glyoxylate Shunt Gene-Expression Dynamics in Mycobacterium tuberculosis“. PLOS Computational Biology 12, Nr. 2 (22.02.2016): e1004741. http://dx.doi.org/10.1371/journal.pcbi.1004741.

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Ruetz, Markus, Gregory C. Campanello, Meredith Purchal, Hongying Shen, Liam McDevitt, Harsha Gouda, Shoko Wakabayashi et al. „Itaconyl-CoA forms a stable biradical in methylmalonyl-CoA mutase and derails its activity and repair“. Science 366, Nr. 6465 (31.10.2019): 589–93. http://dx.doi.org/10.1126/science.aay0934.

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Itaconate is an immunometabolite with both anti-inflammatory and bactericidal effects. Its coenzyme A (CoA) derivative, itaconyl-CoA, inhibits B12-dependent methylmalonyl-CoA mutase (MCM) by an unknown mechanism. We demonstrate that itaconyl-CoA is a suicide inactivator of human and Mycobacterium tuberculosis MCM, which forms a markedly air-stable biradical adduct with the 5′-deoxyadenosyl moiety of the B12 coenzyme. Termination of the catalytic cycle in this way impairs communication between MCM and its auxiliary repair proteins. Crystallography and spectroscopy of the inhibited enzyme are consistent with a metal-centered cobalt radical ~6 angstroms away from the tertiary carbon-centered radical and suggest a means of controlling radical trajectories during MCM catalysis. Mycobacterial MCM thus joins enzymes in the glyoxylate shunt and the methylcitrate cycle as targets of itaconate in pathogen propionate metabolism.

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Pham, Truc V., Andrew S. Murkin, Margaret M. Moynihan, Lawrence Harris, Peter C. Tyler, Nishant Shetty, James C. Sacchettini, Hsiao-ling Huang und Thomas D. Meek. „Mechanism-based inactivator of isocitrate lyases 1 and 2 fromMycobacterium tuberculosis“. Proceedings of the National Academy of Sciences 114, Nr. 29 (05.07.2017): 7617–22. http://dx.doi.org/10.1073/pnas.1706134114.

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Isocitrate lyase (ICL, types 1 and 2) is the first enzyme of the glyoxylate shunt, an essential pathway forMycobacterium tuberculosis(Mtb) during the persistent phase of human TB infection. Here, we report 2-vinyl-d-isocitrate (2-VIC) as a mechanism-based inactivator ofMtbICL1 and ICL2. The enzyme-catalyzed retro-aldol cleavage of 2-VIC unmasks a Michael substrate, 2-vinylglyoxylate, which then forms a slowly reversible, covalent adduct with the thiolate form of active-site Cys191. 2-VIC displayed kinetic properties consistent with covalent, mechanism-based inactivation of ICL1 and ICL2 with high efficiency (partition ratio, <1). Analysis of a complex of ICL1:2-VIC by electrospray ionization mass spectrometry and X-ray crystallography confirmed the formation of the predicted covalentS-homopyruvoyl adduct of the active-site Cys191.

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Held, Gary, und Manuel Goldman. „Pathways of glucose catabolism in the smut fungus Ustilago violacea“. Canadian Journal of Microbiology 32, Nr. 1 (01.01.1986): 56–61. http://dx.doi.org/10.1139/m86-011.

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The pathways of glucose catabolism were examined in haploid and diploid strains of the smut fungus Ustilago violacea. Radiorespirometric studies indicated that both of the haploid mating types and diploid strains of this basidiomycete catabolized glucose through the Embden–Meyerhof and hexose monophosphate shunt pathways. The Entner–Doudoroff pathway was not utilized by any of the strains examined. Radiorespirometric data also suggested functioning of an active tricarboxylic acid cycle. In vitro enzyme assays established the presence in this organism of all the enzymes integral to the operative pathways plus the presence of the enzymes of the glyoxylate cycle. Enzyme activities specific to the Entner–Doudoroff pathway were not detected. No major differences in the routes of glucose dissimilation were found between the two haploid mating types or between haploid and diploid forms of this organism.

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Braeckman, Bart P., und Ineke Dhondt. „Lifespan extension in Caenorhabditis elegans insulin/IGF-1 signalling mutants is supported by non-vertebrate physiological traits“. Nematology 19, Nr. 5 (2017): 499–508. http://dx.doi.org/10.1163/15685411-00003060.

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The insulin/IGF-1 signalling (IIS) pathway connects nutrient levels to metabolism, growth and lifespan in eukaryotes ranging from yeasts to humans, including nematodes such as the genetic model organismCaenorhabditis elegans. The link between ageing and the IIS pathway has been thoroughly studied inC. elegans; upon reduced IIS signalling, a genetic survival program is activated resulting in a drastic lifespan extension. One of the components of this program is the upregulation of antioxidant activity but experiments failed to show a clear causal relation to longevity. However, oxidative damage, such as protein carbonyls, accumulates at a slower pace in long-livedC. elegansmutants with reduced IIS. This is probably not achieved by increased macroautophagy, a process that sequesters cellular components to be eliminated as protein turnover rates are slowed down in IIS mutants. The IIS mutantdaf-2, bearing a mutation in the insulin/IGF-1 receptor, recapitulates the dauer survival program, including accumulation of fat and glycogen. Fat can be converted into glucose and glycogenviathe glyoxylate shunt, a pathway absent in vertebrates. These carbohydrates can be used as substrates for trehalose synthesis, also absent in mammals. Trehalose, a non-reducing homodimer of glucose, stabilises intracellular components and is responsible for almost half of the lifespan extension in IIS mutants. Hence, the molecular mechanisms by which lifespan is extended under reduced IIS may differ substantially between phyla that have an active glyoxylate cycle and trehalose synthesis, such as ecdysozoans and fungi, and vertebrate species such as mammals.

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Xu, Junqi, Yu Chen, Xi Mou, Yu Huang, Shuang Ma, Liyuan Zhang, Yuan Zhang, Quanxin Long, Md Kaisar Ali und Jianping Xie. „Mycobacterium smegmatis msmeg_3314 is involved in pyrazinamide and fluoroquinolones susceptibility via NAD+/NADH dysregulation“. Future Microbiology 15, Nr. 6 (April 2020): 413–26. http://dx.doi.org/10.2217/fmb-2019-0071.

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Aim: To identify and characterize new mycobacterium pyrazinamide (PZA) resistance genes in addition to pncA, rpsA and panD. Materials & methods: To screen a Tn7 M. smegmatis mc2155 transposon library using 50 μM PZA and a PZA hypersensitive mutant (M492) was obtained. MIC was further used to confirm the hypersensitivity of M492 mutant by culturing the mutant in Middlebrook 7H9 liquid medium at 37°C. Results: msmeg_3314 is the gene underlying the hypersensitive phenotype of mutant M492. The observed resistance to PZA and fluoroquinolones involved the alteration of Mycobacterium cell wall permeability and the dissipation of the proton motive force. NAD+/NADH dysregulation and attenuated glyoxylate shunt might underlie the declined scavenging capacity of reactive oxygen species in the msmeg_3314-deficient mutants. Conclusion: msmeg_ 3314 is a novel gene involved in pyrazinamide resistance and might be a new candidate for drugs target.

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Mainguet, Samuel E., Luisa S. Gronenberg, Sio Si Wong und James C. Liao. „A reverse glyoxylate shunt to build a non-native route from C4 to C2 in Escherichia coli“. Metabolic Engineering 19 (September 2013): 116–27. http://dx.doi.org/10.1016/j.ymben.2013.06.004.

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Li, Ning, Bo Zhang, Tao Chen, Zhiwen Wang, Ya-jie Tang und Xueming Zhao. „Directed pathway evolution of the glyoxylate shunt in Escherichia coli for improved aerobic succinate production from glycerol“. Journal of Industrial Microbiology & Biotechnology 40, Nr. 12 (02.10.2013): 1461–75. http://dx.doi.org/10.1007/s10295-013-1342-y.

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Noronha, S. B., H. J. C. Yeh, T. F. Spande und J. Shiloach. „Investigation of the TCA cycle and the glyoxylate shunt inEscherichia coli BL21 and JM109 using13C-NMR/MS“. Biotechnology and Bioengineering 68, Nr. 3 (05.05.2000): 316–27. http://dx.doi.org/10.1002/(sici)1097-0290(20000505)68:3<316::aid-bit10>3.0.co;2-2.

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Negi, Anjali, und Rashmi Sharma. „The significance of persisters in tuberculosis drug discovery: Exploring the potential of targeting the glyoxylate shunt pathway“. European Journal of Medicinal Chemistry 265 (Februar 2024): 116058. http://dx.doi.org/10.1016/j.ejmech.2023.116058.

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Brigham, Christopher J., Charles F. Budde, Jason W. Holder, Qiandong Zeng, Alison E. Mahan, ChoKyun Rha und Anthony J. Sinskey. „Elucidation of β-Oxidation Pathways in Ralstonia eutropha H16 by Examination of Global Gene Expression“. Journal of Bacteriology 192, Nr. 20 (13.08.2010): 5454–64. http://dx.doi.org/10.1128/jb.00493-10.

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ABSTRACT Ralstonia eutropha H16 is capable of growth and polyhydroxyalkanoate production on plant oils and fatty acids. However, little is known about the triacylglycerol and fatty acid degradation pathways of this bacterium. We compare whole-cell gene expression levels of R. eutropha H16 during growth and polyhydroxyalkanoate production on trioleate and fructose. Trioleate is a triacylglycerol that serves as a model for plant oils. Among the genes of note, two potential fatty acid β-oxidation operons and two putative lipase genes were shown to be upregulated in trioleate cultures. The genes of the glyoxylate bypass also exhibit increased expression during growth on trioleate. We observed that single β-oxidation operon deletion mutants of R. eutropha could grow using palm oil or crude palm kernel oil as the sole carbon source, regardless of which operon was present in the genome, but a double mutant was unable to grow under these conditions. A lipase deletion mutant did not exhibit a growth defect in emulsified oil cultures but did exhibit a phenotype in cultures containing nonemulsified oil. Mutants of the glyoxylate shunt gene for isocitrate lyase were able to grow in the presence of oils, while a malate synthase (aceB) deletion mutant grew more slowly than wild type. Gene expression under polyhydroxyalkanoate storage conditions was also examined. Many findings of this analysis confirm results from previous studies by our group and others. This work represents the first examination of global gene expression involving triacylglycerol and fatty acid catabolism genes in R. eutropha.

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Zhao, Hui, Yu Fang, Xiaoyuan Wang, Lei Zhao, Jianli Wang und Ye Li. „Increasing l-threonine production in Escherichia coli by engineering the glyoxylate shunt and the l-threonine biosynthesis pathway“. Applied Microbiology and Biotechnology 102, Nr. 13 (30.04.2018): 5505–18. http://dx.doi.org/10.1007/s00253-018-9024-3.

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Zečić, Aleksandra, und Bart P. Braeckman. „DAF-16/FoxO in Caenorhabditis elegans and Its Role in Metabolic Remodeling“. Cells 9, Nr. 1 (02.01.2020): 109. http://dx.doi.org/10.3390/cells9010109.

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DAF-16, the only forkhead box transcription factors class O (FoxO) homolog in Caenorhabditis elegans, integrates signals from upstream pathways to elicit transcriptional changes in many genes involved in aging, development, stress, metabolism, and immunity. The major regulator of DAF-16 activity is the insulin/insulin-like growth factor 1 (IGF-1) signaling (IIS) pathway, reduction of which leads to lifespan extension in worms, flies, mice, and humans. In C. elegans daf-2 mutants, reduced IIS leads to a heterochronic activation of a dauer survival program during adulthood. This program includes elevated antioxidant defense and a metabolic shift toward accumulation of carbohydrates (i.e., trehalose and glycogen) and triglycerides, and activation of the glyoxylate shunt, which could allow fat-to-carbohydrate conversion. The longevity of daf-2 mutants seems to be partially supported by endogenous trehalose, a nonreducing disaccharide that mammals cannot synthesize, which points toward considerable differences in downstream mechanisms by which IIS regulates aging in distinct groups.

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Vereecke, Danny, Karen Cornelis, Wim Temmerman, Mondher Jaziri, Marc Van Montagu, Marcelle Holsters und Koen Goethals. „Chromosomal Locus That Affects Pathogenicity of Rhodococcus fascians“. Journal of Bacteriology 184, Nr. 4 (15.02.2002): 1112–20. http://dx.doi.org/10.1128/jb.184.4.1112-1120.2002.

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ABSTRACT The gram-positive plant pathogen Rhodococcus fascians provokes leafy gall formation on a wide range of plants through secretion of signal molecules that interfere with the hormone balance of the host. Crucial virulence genes are located on a linear plasmid, and their expression is tightly controlled. A mutant with a mutation in a chromosomal locus that affected virulence was isolated. The mutation was located in gene vicA, which encodes a malate synthase and is functional in the glyoxylate shunt of the Krebs cycle. VicA is required for efficient in planta growth in symptomatic, but not in normal, plant tissue, indicating that the metabolic requirement of the bacteria or the nutritional environment in plants or both change during the interaction. We propose that induced hyperplasia on plants represents specific niches for the causative organisms as a result of physiological alterations in the symptomatic tissue. Hence, such interaction could be referred to as metabolic habitat modification.

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