Two distinct glyceraldehyde‐3‐phosphate dehydrogenases in glycolysis and gluconeogenesis in the archaeon Haloferax volcanii

Tästensen, Julia-Beate; Schönheit, Peter

doi:10.1002/1873-3468.13037

Cited by 14 publications

(16 citation statements)

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“…G3P is an important metabolite of glycolysis and the pentose phosphate pathway. 42 Glycolysis is the main energy source of tumour cells. 43 , 44 The pentose phosphate pathway not only provides 5-ribonucleic acid for the rapid proliferation of tumour cells; in addition, the p53 protein has been reported to inhibit the pentose phosphate pathway by binding glucose-6-phosphate dehydrogenase.…”

Section: Discussionmentioning

confidence: 99%

Discovering Biomarkers in Peritoneal Metastasis of Gastric Cancer by Metabolomics

Pan¹,

Ma²,

Suo³

et al. 2020

OTT

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Background and Objective: Metabolomics has recently been applied in the field of oncology. In this study, we aimed to use metabolomics to explore biomarkers in peritoneal metastasis of gastric cancer. Methods: Peritoneal lavage fluid (PLF) of 65 gastric cancer patients and related clinical data were collected from the First Hospital of Jilin University. The metabolic components were identified by liquid chromatography-mass spectrometry (LC-MS). Total ion current (TIC) spectra, principal component analysis (PCA), and the Student's t-test were used to identify differential metabolites in PLF. A support vector machine (SVM) was used to screen the differential metabolites in PLF with a weight of 100%. Cluster analysis was used to evaluate the similarity between samples. Receiver operating characteristic (ROC) curve analysis was used to assess the diagnostic ability of the metabolites. Univariate and multivariate logistic regression analyses were used to identify potential risk factors for peritoneal metastasis of gastric cancer. Results: We found the differential levels of PLF metabolites by LC-MS, TIC spectra, PCA and the t-test. Cluster analysis showed the co-occurrence of metabolites in the peritoneal metastasis group (p<0.05). ROC analysis showed the diagnostic ability of metabolites (p<0.05). Univariate and multivariate logistic regression analyses showed the potential independent risk factors for peritoneal metastasis in gastric cancer patients (p<0.05). Conclusion: Through the statistical analysis of metabolomics, we found that TG (54:2

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Section: Discussionmentioning

confidence: 99%

Discovering Biomarkers in Peritoneal Metastasis of Gastric Cancer by Metabolomics

Pan¹,

Ma²,

Suo³

et al. 2020

OTT

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“…Glucose degradation to pyruvate in the thermoacidophilic Euryarchaeota Thermoplasma acidophilum and Picrophilus torridus is mediated by a nonphosphorylative version of the ED pathway (13), whereas in various haloarchaea, such as Haloferax volcanii, Haloarcula marismortui, and Halococcus saccharolyticus, glucose degradation is mediated by the semiphosphorylated ED (spED) pathway (14). Recently, Haloferax volcanii has been reported to contain two functionally distinct glyceraldehyde-3-phosphate dehydrogenases that regulate glycolysis and gluconeogenesis (15). Thus, it is well evident that there exists significant diversity in glucose metabolic pathways among Archaea.…”

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confidence: 99%

Unusual Phosphoenolpyruvate (PEP) Synthetase-Like Protein Crucial to Enhancement of Polyhydroxyalkanoate Accumulation in Haloferax mediterranei Revealed by Dissection of PEP-Pyruvate Interconversion Mechanism

Chen

Mitra

Zhang

et al. 2019

Appl Environ Microbiol

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Phosphoenolpyruvate (PEP)/pyruvate interconversion is a major metabolic point in glycolysis and gluconeogenesis and is catalyzed by various sets of enzymes in different Archaea groups. In this study, we report the key enzymes that catalyze the anabolic and catabolic directions of the PEP/pyruvate interconversion in Haloferax mediterranei. The in silico analysis showed the presence of a potassium-dependent pyruvate kinase (PYKHm [HFX_0773]) and two phosphoenol pyruvate synthetase (PPS) candidates (PPSHm [HFX_0782] and a PPS homolog protein named PPS-like [HFX_2676]) in this strain. Expression of the pykHm gene and ppsHm was induced by glycerol and pyruvate, respectively; whereas the pps-like gene was not induced at all. Similarly, genetic analysis and enzyme activities of purified proteins showed that PYKHm catalyzed the conversion from PEP to pyruvate and that PPSHm catalyzed the reverse reaction, while PPS-like protein displayed no function in PEP/pyruvate interconversion. Interestingly, knockout of the pps-like gene led to a 70.46% increase in poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) production. The transcriptome sequencing (RNA-Seq) and quantitative reverse transcription-PCR (qRT-PCR) results showed that many genes responsible for PHBV monomer supply and for PHBV synthesis were upregulated in a pps-like gene deletion strain and thereby improved PHBV accumulation. Additionally, our phylogenetic evidence suggested that PPS-like protein diverged from PPS enzyme and evolved as a distinct protein with novel function in haloarchaea. Our findings attempt to fill the gaps in central metabolism of Archaea by providing comprehensive information about key enzymes involved in the haloarchaeal PEP/pyruvate interconversion, and we also report a high-yielding PHBV strain with great future potentials. IMPORTANCE Archaea, the third domain of life, have evolved diversified metabolic pathways to cope with their extreme habitats. Phosphoenol pyruvate (PEP)/pyruvate interconversion during carbohydrate metabolism is one such important metabolic process that is highly differentiated among Archaea. However, this process is still uncharacterized in the haloarchaeal group. Haloferax mediterranei is a well-studied haloarchaeon that has the ability to produce polyhydroxyalkanoates (PHAs) under unbalanced nutritional conditions. In this study, we identified the key enzymes involved in this interconversion and discussed their differences with their counterparts from other members of the Archaea and Bacteria domains. Notably, we found a novel protein, phosphoenolpyruvate synthetase-like (PPS-like), which exhibited high homology to PPS enzyme. However, PPS-like protein has evolved some distinct sequence features and functions, and strikingly the corresponding gene deletion helped to enhance poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) synthesis significantly. Overall, we have filled the gap in knowledge about PEP/pyruvate interconversion in haloarchaea and reported an efficient strategy for improving PHBV production in H. mediterranei.

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“…This indicates inverse responses of the two GAPDH proteins, with GAPDH type I involved in glycolysis and GAPDH type II involved in gluconeogenesis (12,31). An anabolic role for GAPDH type II is consistent with the absence of GAPDH type II in Halorhabdus, which lacks other identifiable genes for gluconeogenesis (23,31). Most of the haloarchaea that possess GAPDH type II but lack GAPDH type I do not utilize carbohydrates and so would not be expected to perform glycolysis.…”

Section: Resultsmentioning

confidence: 71%

“…volcanii growth on glucose resulted in higher expression of GAPDH type I but repression of GAPDH type II (12,31,51). This indicates inverse responses of the two GAPDH proteins, with GAPDH type I involved in glycolysis and GAPDH type II involved in gluconeogenesis (12,31). An anabolic role for GAPDH type II is consistent with the absence of GAPDH type II in Halorhabdus, which lacks other identifiable genes for gluconeogenesis (23,31).…”

Section: Resultsmentioning

confidence: 80%

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Sucrose Metabolism in Haloarchaea: Reassessment Using Genomics, Proteomics, and Metagenomics

Williams

Allen

Liao

et al. 2019

Appl Environ Microbiol

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The canonical pathway for sucrose metabolism in haloarchaea utilizes a modified Embden-Meyerhof-Parnas pathway (EMP), in which ketohexokinase and 1-phosphofructokinase phosphorylate fructose released from sucrose hydrolysis. However, our survey of haloarchaeal genomes determined that ketohexokinase and 1-phosphofructokinase genes were not present in all species known to utilize fructose and sucrose, thereby indicating that alternative mechanisms exist for fructose metabolism. A fructokinase gene was identified in the majority of fructose- and sucrose-utilizing species, whereas only a small number possessed a ketohexokinase gene. Analysis of a range of hypersaline metagenomes revealed that haloarchaeal fructokinase genes were far more abundant (37 times) than haloarchaeal ketohexokinase genes. We used proteomic analysis ofHalohasta litchfieldiae(which encodes fructokinase) and identified changes in protein abundance that relate to growth on sucrose. Proteins inferred to be involved in sucrose metabolism included fructokinase, a carbohydrate primary transporter, a putative sucrose hydrolase, and two uncharacterized carbohydrate-related proteins encoded in the same gene cluster as fructokinase and the transporter. Homologs of these proteins were present in the genomes of all haloarchaea that use sugars for growth. Enzymes involved in the semiphosphorylative Entner-Doudoroff pathway also had higher abundances in sucrose-grownH. litchfieldiaecells, consistent with this pathway functioning in the catabolism of the glucose moiety of sucrose. The study revises the current understanding of fundamental pathways for sugar utilization in haloarchaea and proposes alternatives to the modified EMP pathway used by haloarchaea for sucrose and fructose utilization.IMPORTANCEOur ability to infer the function that microorganisms perform in the environment is predicated on assumptions about metabolic capacity. When genomic or metagenomic data are used, metabolic capacity is inferred from genetic potential. Here, we investigate the pathways by which haloarchaea utilize sucrose. The canonical haloarchaeal pathway for fructose metabolism involving ketohexokinase occurs only in a small proportion of haloarchaeal genomes and is underrepresented in metagenomes. Instead, fructokinase genes are present in the majority of genomes/metagenomes. In addition to genomic and metagenomic analyses, we used proteomic analysis ofHalohasta litchfieldiae(which encodes fructokinase but lacks ketohexokinase) and identified changes in protein abundance that related to growth on sucrose. In this way, we identified novel proteins implicated in sucrose metabolism in haloarchaea, comprising a transporter and various catabolic enzymes (including proteins that are annotated as hypothetical).

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Two distinct glyceraldehyde‐3‐phosphate dehydrogenases in glycolysis and gluconeogenesis in the archaeon Haloferax volcanii

Cited by 14 publications

References 45 publications

<p>Discovering Biomarkers in Peritoneal Metastasis of Gastric Cancer by Metabolomics</p>

<p>Discovering Biomarkers in Peritoneal Metastasis of Gastric Cancer by Metabolomics</p>

Unusual Phosphoenolpyruvate (PEP) Synthetase-Like Protein Crucial to Enhancement of Polyhydroxyalkanoate Accumulation in Haloferax mediterranei Revealed by Dissection of PEP-Pyruvate Interconversion Mechanism

Sucrose Metabolism in Haloarchaea: Reassessment Using Genomics, Proteomics, and Metagenomics

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