FAIRDOMHubModelsNadine Veithhttps://fairdomhub.org/models/180?version=1SBMLUniversity of HeidelbergFAIRDOMHubIncreasing antibiotic resistance in pathogenic bacteria necessitates the development of new medication strategies. Interfering with the metabolic network of the pathogen can provide novel drug targets but simultaneously requires a deeper and more detailed organism-specific understanding of the metabolism, which is often surprisingly sparse. In light of this, we reconstructed a genome-scale metabolic model of the pathogen Enterococcus faecalis V583. The manually curated metabolic network comprises 642 metabolites and 706 reactions. We experimentally determined metabolic profiles of E. faecalis grown in chemically defined medium in an anaerobic chemostat setup at different dilution rates and calculated the net uptake and product fluxes to constrain the model. We computed growth-associated energy and maintenance parameters and studied flux distributions through the metabolic network. Amino acid auxotrophies were identified experimentally for model validation and revealed seven essential amino acids. In addition, the important metabolic hub of glutamine/glutamate was altered by constructing a glutamine synthetase knockout mutant. The metabolic profile showed a slight shift in the fermentation pattern toward ethanol production and increased uptake rates of multiple amino acids, especially l-glutamine and l-glutamate. The model was used to understand the altered flux distributions in the mutant and provided an explanation for the experimentally observed redirection of the metabolic flux. We further highlighted the importance of gene-regulatory effects on the redirection of the metabolic fluxes upon perturbation. The genome-scale metabolic model presented here includes gene-protein-reaction associations, allowing a further use for biotechnological applications, for studying essential genes, proteins, or reactions, and the search for novel drug targets.Using a genome-scale metabolic model of Enterococcus faecalis V583 to assess amino acid uptake and its impact on central metabolism.Veith Nadine N, Solheim Margrete M, van Grinsven Koen W A KW, Olivier Brett G BG, Levering Jennifer J, Grosseholz Ruth R, Hugenholtz Jeroen J, Holo Helge H, Nes Ingolf I, Teusink Bas B, Kummer Ursula Uscale tissue, Metabolic Process, scale, Genomes, Metabolic, Metabolism, Metabolized, plant peltate hair, peltate hair, Cellular, whole genome, scales, cellular metabolism, metabolism, metabolic, Enterococcus faecalis str. V583.imprinted and ancient gene protein, biochemical pathways, scale tissue, multicellular organism metabolic process, Metabolic Process, scale, biodegradation, Genomes, Metabolic, degradation, Process, catabolism, Processes, plant peltate hair, peltate hair, metabolism resulting in cell growth, Metabolic Concepts, Metabolic Concept, metabolic process resulting in cell growth, whole genome, Metabolic Processes, Anabolism., Ximpact, impact-a, Concept, Metabolic Phenomena, Enterococcus faecalis str. V583, Metabolism Concepts, Metabolism, amino acid uptake, Phenomena, Concepts, IMPACT, imprinted and ancient gene protein homolog, biotransformation, secretion, scales, Metabolism Concept, E430016J11Rik, Phenomenon, Metabolism Phenomena, Catabolism, metabolism, RWDD5, Metabolic Phenomenonbiochemical pathways, scale tissue, Metabolic Process, Aluminum, Resistances, glutamic acid dianion, Grain Alcohol, Materials, single-organism developmental process, Product, postnatal development, Aminosaeure, NetrinA, Metabolic Concepts, Glu, D430049E23Rik, Amino acid, growth and development, Visible Light, protein, 1-hydroxyethane, L-(+)-glutamine, glutamate, Drug Antimicrobial Resistance, alcohol, Drug Resistances, Readability, Ethanol, primary metabolites, L-Glutaminsaeure-5-amid, 2-Aminoglutaric acid, Associations, Aluminum L-Glutamate, Pharmaceutical Product, hnu, Alkohol, Concepts, 2, L-2-aminoglutaramic acid, Metabolism Concept, hel-n1, protein aggregate, animal, Phenomenon, foton, increased, Elkh, E, F15E12_14, Eubacteria, Grain, amino acids, Glutamate Ammonia Ligase, Genomes, catabolism, plant peltate hair, Ethyl, D-Glutamine, Glutamate Ammonia Ligase (ADP), EK6, Q, metabolic process resulting in cell growth, SAP-2, F15E12.14, Sap-2, Aethanol, [CH2Me(OH)], Bacteria Woese et al. 2024, Ligase, neuroendocrine tumour, Enterococcus faecalis str. V583, reaction, TNFSF14, Dehydrated ethanol, Bacteria <bacteria>, Solute carrier family 6 member 2, medicine, Prokaryotae, Pharmaceutical, Glutamate-Ammonia, CT27014, Drug Antimicrobial Resistances, NET1, SLC6A5, biotransformation, Glutaminic acid, Procaryotae, netA, associated, Catabolism, gamma, Glutamin, spiritus vini, Nervous system-specific RNA-binding protein Hel-N1, Elk, ELK, Radiation, hydrogen glutamate, Alcohol, Process, UNQ391/PRO726, Neuronally-expressed EPH-related tyrosine kinase, Aminokarbonsaeure, metabolism resulting in cell growth, L-Glutamic Acid, Light, SAP2, 9330129L11, GLUTAMINE SYNTHETASE, Ethyl alcohol, Microbial, Fermentations, alpha-amino carboxylic acids, neuroendocrine neoplasm, Absolute Alcohol, organism, el-1, LIGHT, Norepinephrine transporter, Potassium Glutamate, EPH-like kinase 6, Genetic Materials, prokaryotes, secretion, Pharmaceutic, HuB, ETHANOL, D Glutamate, ELAV-like neuronal protein 1, [OEtH], Genetic Material, L Glutamine, Visible Radiations, Amino Acid, Acid, Hgln, Visible Radiation, HELN1, whole organism, HVEML, Amino acids, EtOH, growth pattern, non-developmental growth, Hub, HUB, INSDC_feature:gene, whole genome, hEK6, elrB, (S)-2, alcohol etilico, Methylcarbinol, (D)-Isomer, L-glutamic acid gamma-amide, L-Glutamic acid, DmelCG18657, light quantum, Antimicrobial Drug Resistance, Material, metabolites, Koerper, 2-ammoniopentanedioate, D-Glutamate, p45, Cistron, Acids, hub, Antimicrobial Resistance, Prokaryota, accessory, DL-Glutamic acid, Glutamine, glutamic acid, AW488255, GLUTAMINE, multi-cellular organism, 2-aminopentanedioate, Processes, 5-diamino-5-oxopentanoic acid, peltate hair, Drug Antimicrobial, etanol, Aminocarbonsaeure, secondary metabolites, Levoglutamide, ATGSR2, Gene, eubacteria, alpha-amino acid, Metabolic Processes, (2S)-2-amino-4-carbamoylbutanoic acid, protein-containing complex, elavl2, Glutamine Synthetase, supernumerary, Nervous system-specific RNA-binding protein Mel-N1, Aluminum L Glutamate, Ly113, netrin, Antimicrobial Drug Resistances, Glutaminsaeure-5-amid, Aethylalkohol, Antibiotic Resistance, Hek6, Metabolism, Gene Products, Antibiotic, Cek6, Bacteriobiota, 2-Aminoglutaramic acid, Metabolism Phenomena, heln1, ENSMUSG00000074119, Drugs, Glutamic acid, ERP, APUDoma, Erp, glutamine synthase clone F11, pattern, Genetic, distribution, Absolute, Lichtquant, (2S)-2, ethanol, Tyrosine-protein kinase receptor EPH-2, Metabolic Concept, Visible, Maintenances, Monera, glutamate(2-), L-Glutamate:ammonia ligase (ADP-forming), Bacteria (ex Cavalier-Smith 1987), C2H5OH, drugs, 2.7.10.1, Pharmaceuticals., Etrp, photon, L-Glutamine, NAT1, fungi, species, TR2, Preparation, NET, Net, Potassium, Pharmaceuticals, Products, bacteria, C130099E04Rik, degradation, body, protein complex, HEL-N1, drug, Proteins, EPH tyrosine kinase 2, Antimicrobial Resistances, glutamate(1-), whole body, alpha-amino acids, L-2-Aminoglutaramic acid, neuroendocrine tumor, CD258, Cistrons, net, Concept, Metabolic Phenomena, development, Metabolism Concepts, uptake, native protein, Glutamate, Protein, Phenomena, Resistance, Glutamic Acid, alcool ethylique, Glutamic acid 5-amide, Synthetase, L-Glutamin, scales, Glutaminsaeure, metabolism, L-Glutamate, Metabolic Phenomenon, L Glutamic Acid, Radiations, Ethyl Alcohol, multicellular organism metabolic process, DL-Glutaminic acid, 2-aminopentanedioic acid, biodegradation, scale, xel-1, Pharmaceutic Preparations, Metabolic, Glutamic acid amide, HVEM-L, increased number, postnatal growth, Photoradiation, metabolite, Understanding, Amino, CG18657, LTg, Hu-antigen B, Drug, Protein Gene Products, present in greater numbers in organism, Gene Proteins, glutamic acid monoanion, Preparations, Xel-1, 2-amino-4-carbamoylbutanoic acid, hydroxyethane, Photoradiations, D Glutamine, EPHT2, prokaryote, L Glutamate, glutamic acid gamma-amide, Pharmaceutical Products, growth, netrin A, mel-N1, Pharmaceutical Preparation, Anabolismscale tissue, Metabolic Process, scale, Genomes, Metabolic, Metabolism, Metabolized, plant peltate hair, peltate hair, Cellular, whole genome, scales, cellular metabolism, metabolism, metabolic, Enterococcus faecalis str. V583.falseGenome-scale metabolic model of Enterococcus faecalis V583Genome-scale metabolic model of Enterococcus faecalis V5832015-10-012015-10-012015-10-012015-10-0118025527553