Legionella pneumophila
            CsrA regulates a metabolic switch from amino acid to glycerolipid metabolism

Legionella pneumophila CsrA plays a crucial role in the life-stage-specific expression of virulence phenotypes and metabolic activity. However, its exact role is only partly known. To elucidate how CsrA impacts L. pneumophila metabolism we analysed the CsrA depended regulation of metabolic functions by comparative 13 C-isotopologue profiling and oxygen consumption experiments of a L. pneumophila wild-type (wt) strain and its isogenic csrA − mutant. We show that a csrA − mutant has significantly lower respiration rates when serine, alanine, pyruvate, α-ketoglutarate or palmitate is the sole carbon source. By contrast, when grown in glucose or glycerol, no differences in respiration were detected. Isotopologue profiling uncovered that the transfer of label from [U- 13 C 3 ]serine via pyruvate into the citrate cycle and gluconeogenesis was lower in the mutant as judged from the labelling patterns of protein-derived amino acids, cell-wall-derived diaminopimelate, sugars and amino sugars and 3-hydroxybutyrate derived from polyhydroxybutyrate (PHB). Similarly, the incorporation of [U- 13 C 6 ]glucose via the glycolysis/Entner–Doudoroff (ED) pathway but not via the pentose phosphate pathway was repressed in the csrA − mutant. On the other hand, fluxes due to [U- 13 C 3 ]glycerol utilization were increased in the csrA − mutant. In addition, we showed that exogenous [1,2,3,4- 13 C 4 ]palmitic acid is efficiently used for PHB synthesis via 13 C 2 -acetyl-CoA. Taken together, CsrA induces serine catabolism via the tricarboxylic acid cycle and glucose degradation via the ED pathway, but represses glycerol metabolism, fatty acid degradation and PHB biosynthesis, in particular during exponential growth. Thus, CsrA has a determining role in substrate usage and carbon partitioning during the L. pneumophila life cycle and regulates a switch from amino acid usage in replicative phase to glycerolipid usage during transmissive growth.

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Rewiring of glycerol metabolism in Escherichia coli for effective production of recombinant proteins

Biotechnology for Biofuels ◽

10.1186/s13068-020-01848-z ◽

2020 ◽

Vol 13 (1) ◽

Author(s):

Chung-Jen Chiang ◽

Yi-Jing Ho ◽

Mu-Chen Hu ◽

Yun-Peng Chao

Keyword(s):

Escherichia Coli ◽

Crude Glycerol ◽

Metabolic Flux ◽

Raw Materials ◽

Tricarboxylic Acid Cycle ◽

Cost Effective ◽

Fold Increase ◽

Pentose Phosphate ◽

Glycerol Metabolism ◽

Related Field

Abstract Background The economic viability of a protein-production process relies highly on the production titer and the price of raw materials. Crude glycerol coming from the production of biodiesel is a renewable and cost-effective resource. However, glycerol is inefficiently utilized by Escherichia coli. Results This issue was addressed by rewiring glycerol metabolism for redistribution of the metabolic flux. Key steps in central metabolism involving the glycerol dissimilation pathway, the pentose phosphate pathway, and the tricarboxylic acid cycle were pinpointed and manipulated to provide precursor metabolites and energy. As a result, the engineered E. coli strain displayed a 9- and 30-fold increase in utilization of crude glycerol and production of the target protein, respectively. Conclusions The result indicates that the present method of metabolic engineering is useful and straightforward for efficient adjustment of the flux distribution in glycerol metabolism. The practical application of this methodology in biorefinery and the related field would be acknowledged.

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Glutamate Metabolism in Plant Disease and Defense: Friend or Foe?

Molecular Plant-Microbe Interactions ◽

10.1094/mpmi-07-12-0176-cr ◽

2013 ◽

Vol 26 (5) ◽

pp. 475-485 ◽

Cited By ~ 96

Author(s):

Hamed Soren Seifi ◽

Jonas Van Bockhaven ◽

Geert Angenon ◽

Monica Höfte

Keyword(s):

Amino Acid ◽

Redox Regulation ◽

Tricarboxylic Acid Cycle ◽

Glutamate Metabolism ◽

Metabolic State ◽

Resistance Response ◽

Metabolic Functions ◽

Amino Acid Utilization ◽

Toxin Secretion ◽

Cycle Dependent

Plant glutamate metabolism (GM) plays a pivotal role in amino acid metabolism and orchestrates crucial metabolic functions, with key roles in plant defense against pathogens. These functions concern three major areas: nitrogen transportation via the glutamine synthetase and glutamine-oxoglutarate aminotransferase cycle, cellular redox regulation, and tricarboxylic acid cycle-dependent energy reprogramming. During interactions with pathogens, the host GM is markedly altered, leading to either a metabolic state, termed “endurance”, in which cell viability is maintained, or to an opposite metabolic state, termed “evasion”, in which the process of cell death is facilitated. It seems that endurance-natured modulations result in resistance to necrotrophic pathogens and susceptibility to biotrophs, whereas evasion-related reconfigurations lead to resistance to biotrophic pathogens but stimulate the infection by necrotrophs. Pathogens, however, have evolved strategies such as toxin secretion, hemibiotrophy, and selective amino acid utilization to exploit the plant GM to their own benefit. Collectively, alterations in the host GM in response to different pathogenic scenarios appear to function in two opposing ways, either backing the ongoing defense strategy to ultimately shape an efficient resistance response or being exploited by the pathogen to promote and facilitate infection.

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Key metabolic pathways involved in seed primary physiological dormancy maintenance of Korean pine seed

10.1101/2021.02.08.430286 ◽

2021 ◽

Author(s):

Yuan Song ◽

Xiaoye Gao

Keyword(s):

Seed Coat ◽

Tricarboxylic Acid Cycle ◽

Pentose Phosphate ◽

Metabolic Changes ◽

Korean Pine ◽

Metabolic Switch ◽

Operation Rate ◽

Physiological Dormancy ◽

Radicle Protrusion ◽

Stage Embryo

ABSTRACTThe metabolic changes that occurred during either cold stratification or after-ripen treatment, and in both dormant seeds and after-ripened seeds either under the dry state or during imbibition have been extensively explored. Much less is known about those present in both dormant seeds and cold stratified seeds during the same period of incubation under favorable germination conditions. Metabolite composition was investigated in both embryo and megagametophyte of primary physiological dormant seeds (PPDS) of Pinus Koreansis collected at 0 week, 1 week, 2 weeks, 4 weeks and 6 weeks of incubation, and of cold stratified seeds with released primary physiological dormancy (RPPDS) sampled at 0 week and 1 week of incubation, seed coat rupture stage and radicle protrusion stage. Embryo contained higher levels of most metabolites compared to megagametophyte. Strong metabolic changes occurred at 1 week and 4 weeks of incubation in PPDS, with most metabolites were significantly accumulated in 4-weeks-incubated PPDS. A larger metabolic switch was found in RPPDS between 1-week-incubation and seed coat rupture stage. Especially, there was a significant major decrease in the relative levels of most phosphorylated sugars and amino acids. The carbohydrate metabolism, especially pentose phosphate pathway and tricarboxylic acid cycle were more active pathways in the embryos of 4-weeks-incubated PPDS, but the operation rate of most amino acid metabolism was lower compared to 1-week-incubated RPPDS. We suggest that a larger metabolic switch in the embryo of PPDS after 4 weeks of incubation may assist in maintaining primary dormancy.One-sentence summaryA larger metabolic switch in dormant seeds after 4 weeks of incubation under favorable conditions for germination may maintain primary physiological dormancy of Korean pine seeds.

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An Oral Load of [13C3]Glycerol and Blood NMR Analysis Detect Fatty Acid Esterification, Pentose Phosphate Pathway, and Glycerol Metabolism through the Tricarboxylic Acid Cycle in Human Liver

Journal of Biological Chemistry ◽

10.1074/jbc.m116.742262 ◽

2016 ◽

Vol 291 (36) ◽

pp. 19031-19041 ◽

Cited By ~ 10

Author(s):

Eunsook S. Jin ◽

A. Dean Sherry ◽

Craig R. Malloy

Keyword(s):

Fatty Acid ◽

Pentose Phosphate Pathway ◽

Human Liver ◽

Tricarboxylic Acid Cycle ◽

Tricarboxylic Acid ◽

Pentose Phosphate ◽

Glycerol Metabolism ◽

Nmr Analysis ◽

Acid Cycle ◽

Acid Esterification

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Effect of Huangqin Tang on Urine Metabolic Profile in Rats with Ulcerative Colitis Based on UPLC-Q-Exactive Orbitrap MS

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2020/1874065 ◽

2020 ◽

Vol 2020 ◽

pp. 1-11

Author(s):

Dunfang Wang ◽

Xuran Ma ◽

Shanshan Guo ◽

Yanli Wang ◽

Tao Li ◽

...

Keyword(s):

Ulcerative Colitis ◽

Fatty Acids ◽

Amino Acid ◽

Amino Acid Metabolism ◽

Acid Metabolism ◽

Unsaturated Fatty Acids ◽

Tricarboxylic Acid Cycle ◽

Tca Cycle ◽

Q Exactive ◽

Therapeutic Mechanisms

As a classic prescription, Huangqin Tang (HQT) has been widely applied to treat ulcerative colitis (UC), although its pharmacological mechanisms are not clear. In this study, urine metabolomics was first analysed to explore the therapeutic mechanisms of HQT in UC rats induced by TNBS. We identified 28 potential biomarkers affected by HQT that might cause changes in urine metabolism in UC rats, mapped the network of metabolic pathways, and revealed how HQT affects metabolism of UC rats. The results showed that UC affects amino acid metabolism and biosynthesis of unsaturated fatty acids and impairs the tricarboxylic acid cycle (TCA cycle). UC induced inflammatory and gastrointestinal reactions by inhibiting the transport of fatty acids and disrupting amino acid metabolism. HQT plays key roles via regulating the level of biomarkers in the metabolism of amino acids, lipids, and so on, normalizing metabolic disorders. In addition, histopathology and other bioinformatics analysis further confirm that HQT altered UC rat physiology and pathology, ultimately affecting metabolic function of UC rats.

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The relevance of adhesion G protein-coupled receptors in metabolic functions

Biological Chemistry ◽

10.1515/hsz-2021-0146 ◽

2021 ◽

Vol 0 (0) ◽

Author(s):

Isabell Kaczmarek ◽

Tomáš Suchý ◽

Simone Prömel ◽

Torsten Schöneberg ◽

Ines Liebscher ◽

...

Keyword(s):

G Protein ◽

Drug Targets ◽

Metabolic Diseases ◽

Current Knowledge ◽

G Protein Coupled Receptors ◽

Specific Expression ◽

Physiological Functions ◽

Metabolic Functions ◽

Central Nervous Systems ◽

G Protein Coupled

Abstract G protein-coupled receptors (GPCRs) modulate a variety of physiological functions and have been proven to be outstanding drug targets. However, approximately one-third of all non-olfactory GPCRs are still orphans in respect to their signal transduction and physiological functions. Receptors of the class of Adhesion GPCRs (aGPCRs) are among these orphan receptors. They are characterized by unique features in their structure and tissue-specific expression, which yields them interesting candidates for deorphanization and testing as potential therapeutic targets. Capable of G-protein coupling and non-G protein-mediated function, aGPCRs may extend our repertoire of influencing physiological function. Besides their described significance in the immune and central nervous systems, growing evidence indicates a high importance of these receptors in metabolic tissue. RNAseq analyses revealed high expression of several aGPCRs in pancreatic islets, adipose tissue, liver, and intestine but also in neurons governing food intake. In this review, we focus on aGPCRs and their function in regulating metabolic pathways. Based on current knowledge, this receptor class represents high potential for future pharmacological approaches addressing obesity and other metabolic diseases.

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Malonyl-proteome profiles of Staphylococcus aureus reveal lysine malonylation modification in enzymes involved in energy metabolism

Proteome Science ◽

10.1186/s12953-020-00169-1 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Yanan Shi ◽

Jingjing Zhu ◽

Yan Xu ◽

Xiaozhao Tang ◽

Zushun Yang ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Energy Metabolism ◽

Active Sites ◽

Current Knowledge ◽

Tricarboxylic Acid Cycle ◽

Protein A ◽

Pentose Phosphate ◽

Post Translational Modification ◽

Bacterial Physiology ◽

Dihydrolipoyl Dehydrogenase

Abstract Background Protein lysine malonylation, a novel post-translational modification (PTM), has been recently linked with energy metabolism in bacteria. Staphylococcus aureus is the third most important foodborne pathogen worldwide. Nonetheless, substrates and biological roles of malonylation are still poorly understood in this pathogen. Results Using anti-malonyl-lysine antibody enrichment and high-resolution LC-MS/MS analysis, 440 lysine-malonylated sites were identified in 281 proteins of S. aureus strain. The frequency of valine in position − 1 and alanine at + 2 and + 4 positions was high. KEGG pathway analysis showed that six categories were highly enriched, including ribosome, glycolysis/gluconeogenesis, pentose phosphate pathway (PPP), tricarboxylic acid cycle (TCA), valine, leucine, isoleucine degradation, and aminoacyl-tRNA biosynthesis. In total, 31 malonylated sites in S. aureus shared homology with lysine-malonylated sites previously identified in E. coli, indicating malonylated proteins are highly conserved among bacteria. Key rate-limiting enzymes in central carbon metabolic pathways were also found to be malonylated in S. aureus, namely pyruvate kinase (PYK), 6-phosphofructokinase, phosphoglycerate kinase, dihydrolipoyl dehydrogenase, and F1F0-ATP synthase. Notably, malonylation sites were found at or near protein active sites, including KH domain protein, thioredoxin, alanine dehydrogenase (ALD), dihydrolipoyl dehydrogenase (LpdA), pyruvate oxidase CidC, and catabolite control protein A (CcpA), thus suggesting that lysine malonylation may affect the activity of such enzymes. Conclusions Data presented herein expand the current knowledge on lysine malonylation in prokaryotes and indicate the potential roles of protein malonylation in bacterial physiology and metabolism.

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Novel Antarctic yeast adapts to cold by switching energy metabolism and increasing small RNA synthesis

The ISME Journal ◽

10.1038/s41396-021-01030-9 ◽

2021 ◽

Author(s):

D. Touchette ◽

I. Altshuler ◽

C. Gostinčar ◽

P. Zalar ◽

I. Raymond-Bouchard ◽

...

Keyword(s):

Ethanol Production ◽

Ethanol Fermentation ◽

Phylogenetic Analyses ◽

Regulation Of Gene Expression ◽

Pentose Phosphate ◽

Metabolic Switch ◽

Antarctic Yeast ◽

Fungal Adaptation ◽

Pentose Phosphate Pathways ◽

Post Transcriptional Regulation

AbstractThe novel extremophilic yeast Rhodotorula frigidialcoholis, formerly R. JG1b, was isolated from ice-cemented permafrost in University Valley (Antarctic), one of coldest and driest environments on Earth. Phenotypic and phylogenetic analyses classified R. frigidialcoholis as a novel species. To characterize its cold-adaptive strategies, we performed mRNA and sRNA transcriptomic analyses, phenotypic profiling, and assessed ethanol production at 0 and 23 °C. Downregulation of the ETC and citrate cycle genes, overexpression of fermentation and pentose phosphate pathways genes, growth without reduction of tetrazolium dye, and our discovery of ethanol production at 0 °C indicate that R. frigidialcoholis induces a metabolic switch from respiration to ethanol fermentation as adaptation in Antarctic permafrost. This is the first report of microbial ethanol fermentation utilized as the major energy pathway in response to cold and the coldest temperature reported for natural ethanol production. R. frigidialcoholis increased its diversity and abundance of sRNAs when grown at 0 versus 23 °C. This was consistent with increase in transcription of Dicer, a key protein for sRNA processing. Our results strongly imply that post-transcriptional regulation of gene expression and mRNA silencing may be a novel evolutionary fungal adaptation in the cryosphere.

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