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evolution
dihydrolipoamide dehydrogenase is a member of the disulfide oxidoreductase family
evolution
dihydrolipoamide dehydrogenase is a member of the disulfide oxidoreductase family
evolution
dihydrolipoamide dehydrogenase is a member of the disulfide oxidoreductase family
evolution
E3 belongs to the pyridine nucleotide-disulfide oxidoreductase family along with glutathione reductase (GR), thioredoxin reductase, mercuric reductase and trypanothione reductase
evolution
residue Cys50 is absolutely conserved, Cys50 is a component of the very long a-helix structure 2, which is composed of 25 amino acids. Residue Cys50 forms an active disulfide center with Cys45
evolution
residue H329 is absolutely conserved, H329 329 is a part of the long alpha-helix 8, which is composed of 16 amino acids and is a component of the central domain. His329 is also located near FAD and the active disulfide center between Cys45 and Cys50, which are essential to the catalytic activity of human E3
evolution
residues Pro156 and Pro303 are highly conserved
malfunction
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enhanced arsenate and arsenite sensitivity is due to the disruption of the plastidial LPD1 and LPD2 genes
malfunction
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the homozygous deletion mutant lpd1/lpd1 is unable to grow on non-fermentable carbon sources including glycerol, ethanol, acetate, and citrate. In addition, the lpd1/lpd1 strain exhibits a slow-growth phenotype on glucose-containing media and a marked sensitivity to 0.5 mM of hydrogen peroxide and shows filamentation defects
malfunction
as a common component in three 2-oxo acid dehydrogenase, a decrease in E3 activity affects the activities of all three complexes, which leads to increased urinary excretion of 2-oxo acids, elevated blood lactate, pyruvate, and branched chain amino acids. Patients with an E3 deficiency normally die young because an E3 deficiency is a critical genetic defect affecting the central nervous system. A deficiency in E3 results in Leigh syndrome with recurrent episodes of hypoglycemia and ataxia, permanent lactic acidaemia, and mental retardation. A C45A mutation results in a large decrease in human E3 activity and changes in the spectroscopic properties of human E3
malfunction
metabolic acclimation of Arabidopsis thaliana to arsenate is sensitized by the loss of mitochondrial lipoamide dehydrogenase2. Both arsenate and arsenite inhibit root elongation, decreased seedling size and increase anthocyanin production more profoundly in knockout mutants than in wild-type seedlings, arsenite seems to be the mediator of the observed phenotypes
malfunction
pathogenic amino acid substitutions of the common E3 component (hE3) of the human 2-oxoglutarate dehydrogenase and the pyruvate dehydrogenase complexes lead to severe metabolic diseases (E3 deficiency), which usually manifest themselves in cardiological and/or neurological symptoms and often cause premature death. Determination of structural alterations induced by ten disease-causing mutations of human dihydrolipoamide dehydrogenase involved in E3 deficiency, using hydrogen/deuterium-exchange mass spectrometry
malfunction
pathogenic mutations of hLADH cause severe metabolic diseases (atypical forms of E3 deficiency) that often escalate to cardiological or neurological presentations and even premature death. The pathologies are generally accompanied by lactic acidosis. hLADH presents a distinct conformation under acidosis (pH 5.5-6.8) with lower physiological activity and the capacity of generating reactive oxygen species (ROS). Molecular dynamics simulation of the structural changes induced in the low-pH conformation of hLADH by five pathogenic mutations of hLADH. Determination of structures of these disease-causing mutants of hLADH, overview
malfunction
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pathogenic mutations of LADH cause severe metabolic disturbances, called E3 deficiency that often involve cardiological and neurological symptoms and premature death. Some of the known pathogenic mutations augment the reactive oxygen species (ROS) generation capacity of LADH, which may contribute to the clinical presentations. Structural changes are likely to turn the physiological LADH conformation to its ROS-generating conformation
malfunction
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Pfae3 is deleted from Plasmodium falciparum and although the mutants are viable, they display a highly synchronous growth phenotype during intra-erythrocytic development. The mutants also show changes in the expression of some mitochondrial and antioxidant proteins suggesting that deletion of Pfae3 impacts on the parasite's metabolic function with downstream effects on the parasite's redox homoeostasis and cell cycle
malfunction
chronic inhibition of the enzyme can attenuate oxidative stress in type 2 diabetes
malfunction
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the homozygous deletion mutant lpd1/lpd1 is unable to grow on non-fermentable carbon sources including glycerol, ethanol, acetate, and citrate. In addition, the lpd1/lpd1 strain exhibits a slow-growth phenotype on glucose-containing media and a marked sensitivity to 0.5 mM of hydrogen peroxide and shows filamentation defects
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metabolism
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enzyme is inactivated by complex III- but not complex I-derived reactive oxygen species, and the accompanying loss of activity due to the inactivation can be restored by cysteine and glutathione. H2O2 instead of superoxide anion is responsible for the inactivation, and protein sulfenic acid formation is associated with the loss of enzymatic activity
metabolism
dihydrolipoamide dehydrogenase (E3) is a component of three different catabolic multienzyme complexes that oxidize pyruvate, 2-oxoglutarate, or glycine, where E3 catalyzes the final step in a sequence of oxidative reactions
metabolism
dihydrolipoamide dehydrogenase (E3) is a component of three different catabolic multienzyme complexes that oxidize pyruvate, 2-oxoglutarate, or glycine, where E3 catalyzes the final step in a sequence of oxidative reactions
metabolism
dihydrolipoamide dehydrogenase (E3) is a component of three different catabolic multienzyme complexes that oxidize pyruvate, 2-oxooglutarate, or glycine, where E3 catalyzes the final step in a sequence of oxidative reactions
metabolism
the enzyme is a key enzyme in oxidative metabolism
physiological function
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effects of insulin treatment on HuC/HuD myoenteric neurons, NADH diaphorase, and nNOS-positive myoenteric neurons of the duodenum of adult rats with acute diabetes is investigated: The density of NADH diaphorase-positive neurons in animals from the diabetic group and in the insulin treated diabetic group is greater than in the control group, indicating that short-term diabetes increases the activity of respiratory chain enzymes
physiological function
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last step of glycine cleavage system
physiological function
dihydrolipoamide dehydrogenase is a FAD-linked subunit of 2-oxooglutarate, pyruvate and branched-chain amino acid dehydrogenases and the glycine cleavage system, transfering electrons from the dihydrolipoic acid prosthetic group to the NAD+ cofactor via its FAD center
physiological function
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dihydrolipoamide dehydrogenase Lpd1 is a catalytic component of pyruvate dehydrogenase complex. LPD1 is required for filamentous growth under a serum-containing hyphal-inducing condition
physiological function
LPD is a useful biocatalyst for regenerating NAD+
physiological function
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plastidial LPD expression quantitatively controls Arabidopsis arsenate sensitivity
physiological function
Starkeyomyces koorchalomoides
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the protein acetyltransferase activity of LADH can be attributed as a moonlighting function of the enzyme
physiological function
enzyme is surface-exposed and contributes to survival of Pseudomonas aeruginosa in human serum. Enzyme binds the four human plasma proteins, Factor H, factor H-like protein-1, complement factor H-related protein 1, and plasminogen. Factor H contacts the enzyme via short consensus repeats 7 and 18-20. Factor H, factor H-like protein-1, and plasminogen when bound to enzyme are functionally active. Bacterial survival is reduced when the enzyme is blocked on the surface prior to challenge with human serum. Similarly, bacterial survival is reduced up to 84% when the bacteria are challenged with complement active serum depleted of factor H, factor H-like protein-1, and complement factor H-related protein 1
physiological function
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like the raffinose ATP-binding protein RafK, the presence of the enzyme also activates the expression of raf operon genes. Enzyme-negative pneumococci show a significantly decreased expression of aga and rafEFG, but dihydrolipoamide dehydrogenase does not regulate rafK or the putative regulatory genes rafR and rafS. Dihydrolipoamide dehydrogenase also binds directly to RafK both in vitro and in vivo, indicating the possibility that dihydrolipoamide dehydrogenase regulates raffinose transport by a direct interaction with the regulatory domain of the transporter
physiological function
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lipoamide dehydrogenase-deficient Mycobacterium tuberculosis is severely attenuated in wild type and immunodeficient mice. When dihydrolipoamide acyltransferase is absent, Mycobacterium tuberculosis upregulates an lipoamide dehydrogenase-dependent branched chain keto-acid dehydrogenase encoded by pdhA, pdhB, pdhC and lpdC. Without lipoamide dehydrogenase, Mycobacterium tuberculosis cannot metabolize branched chain amino acids and potentially toxic branched chain intermediates accumulate. Mycobacterium tuberculosis deficient in both dihydrolipoamide acyltransferase and pdhC phenocopies lipoamide Mycobycterium tuberculosis
physiological function
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RNA interference or the deletion of both alleles of lipoamide dehydrogenase in bloodstream Trypanosoma brucei results in an absolute requirement for exogenous thymidine. In the absence of thymidine, lipdh-/- parasites show a severely altered morphology and cell cycle distribution. Lipdh-/- cells are unable to infect mice. Degradation of branched-chain amino acids takes place but is dispensable. In cultured bloodstream - but not procyclic - African trypanosomes, the total cellular concentration of lipoamide dehydrogenase increases with increasing cell densities. In procyclic parasites, lipoamide dehydrogenasemRNA depletion causes an even stronger proliferation defect that is not reversed by presence of thymidine
physiological function
dihydrolipoamide dehydrogenase (LipDH) transfers two electrons from dihydrolipoamide to NAD+ mediated by FAD. Since this reaction is the final step of a series of catalytic reaction of pyruvate dehydrogenase multi-enzyme complex (PDC), LipDH is a key enzyme to maintain the fluent metabolic flow
physiological function
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dihydrolipoamide dehydrogenase is a component in the pyruvate-, 2-oxooglutarate- and branched-chain oxoacid dehydrogenase complexes and in the glycine cleavage system
physiological function
dihydrolipoamide dehydrogenase is the E3 subunit of the mitochondrial pyruvate dehydrogenase complex, rearrangement of mitochondrial pyruvate dehydrogenase subunit dihydrolipoamide dehydrogenase protein-protein interactions by the MDM2 ligand nutlin-3
physiological function
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dihydrolipoamide dehydrogenase of Escherichia coli is a bacterial enzyme that is involved in the central metabolism and shared in common between the pyruvate dehydrogenase and 2-oxoglutarate dehydrogenase complexes. The presence of oligomeric forms of the enzyme is determined by the multifunctionality of LpD in the cell, in particular, the required stoichiometry in the complexes. The E3 enzyme activity is essential for aerobic respiration. Dihydrolipoamide dehydrogenase plays an equally important role in anaerobic organisms, since this enzyme is involved in the synthesis of branched-chain keto and amino acids
physiological function
E3 catalyzes the reoxidation of the dihydrolipoyl prosthetic group attached to the lysyl residue(s) of the acyltransferase components of these dehydrogenase complexes
physiological function
E3 is an essential component in pyruvate, 2-oxoglutarate and branched-chain 2-oxo acid dehydrogenase complexes. E3 catalyzes the reoxidation of a dihydrolipoyl prosthetic group attached to the lysyl residue(s) of the acyltransferase components of the three 2-oxo acid dehydrogenase complexes
physiological function
human dihydrolipoamide dehydrogenase is a flavoenzyme component (E3) of the human 2-oxoglutarate dehydrogenase complex and few other dehydrogenase complexes
physiological function
in vivo, the dihydrolipoamide dehydrogenase component (E3) is associated with the pyruvate, 2-oxoglutarate, and glycine dehydrogenase complexes. The pyruvate dehydrogenase (PDH) complex connects the glycolytic flux to the tricarboxylic acid cycle and is central to the regulation of primary metabolism. Regulation of PDH via regulation of the E3 component by the NAD+/NADH ratio represents one of the important physiological control mechanisms of PDH activity. Steady-state distributions of enzyme redox states as a function of lipoamide/ dihydrolipoamide, NAD+/NADH, and pH, modelling, overview
physiological function
in vivo, the dihydrolipoamide dehydrogenase component (E3) is associated with the pyruvate, 2-oxoglutarate, and glycine dehydrogenase complexes. The pyruvate dehydrogenase (PDH) complex connects the glycolytic flux to the tricarboxylic acid cycle and is central to the regulation of primary metabolism. Regulation of PDH via regulation of the E3 component by the NAD+/NADH ratio represents one of the important physiological control mechanisms of PDH activity. Steady-state distributions of enzyme redox states as a function of lipoamide/ dihydrolipoamide, NAD+/NADH, and pH, modelling, overview
physiological function
in vivo, the dihydrolipoamide dehydrogenase component (E3) is associated with the pyruvate, 2-oxoglutarate, and glycine dehydrogenase complexes. The pyruvate dehydrogenase (PDH) complex connects the glycolytic flux to the tricarboxylic acid cycle and is central to the regulation of primary metabolism. Regulation of PDH via regulation of the E3 component by the NAD+/NADH ratio represents one of the important physiological control mechanisms of PDH activity. Steady-state distributions of enzyme redox states as a function of lipoamide/ dihydrolipoamide, NAD+/NADH, and pH, modelling, overview
physiological function
LpdG, not LpdV and Lpd3, is the primary DLDH of the Pseudomonas aeruginosa PA14 pyruvate dehydrogenase, and is the enzymatically relevant DLDH for both pyruvate and 2-oxoglutarate dehydrogenase
physiological function
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pyruvate dehydrogenase complex, PDC, is a multi-enzyme complex comprising an E1, pyruvate decarboxylase, an E2, dihydrolipomide acetyltransferase, and an E3, dihydrolipoamide dehydrogenase. Plasmodium PDC is essential for parasite survival in the mosquito vector and for late liver stage development in the human host
physiological function
the enzyme DLDH shows titanium dioxide (TiO2) binding capability. The putative TiO2-binding regions of both the bacterial and human enzymes are found to contain a CHED (Cys, His, Glu, Asp) motif, which has been shown to participate in metal-binding sites in proteins. The binding of hDLDH to TiO2 at physiological pH values and above is nonelectrostatic and involves chelating/coordinative interactions of DLDH acidic residues with the oxide, docking calculations. Native DLDH is tethered to the pyruvate dehydrogenase complex by interactions with a mediatory protein, E3 binding protein (E3BP), via a region that overlaps with the putative TiO2?binding site, involving V347, H348, D413, E437, Y438, G439, E443, D444, and R447
physiological function
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the enzyme shows titanium dioxide (TiO2) binding capability. The putative TiO2-binding regions of both the bacterial and human enzymes are found to contain a CHED (Cys, His, Glu, Asp) motif, which has been shown to participate in metal-binding sites in proteins. The binding of rhDLDH to TiO2 at physiological pH values and above is nonelectrostatic and involves chelating/coordinative interactions of DLDH acidic residues with the oxide, docking calculations
physiological function
the enzyme, as the E3 component of the pyruvate decarboxylase complex, has reactive oxygen species generating activity
physiological function
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the enzyme is involved in adhesion to polystyrene as well as coelomocytes and other tissues like body wall, tentacle, muscle, respiratory tree and intestine from sea cucumber Apostichopus japonicas
physiological function
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the enzyme regulates cystine deprivation-induced ferroptosis in head and neck cancer
physiological function
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enzyme is surface-exposed and contributes to survival of Pseudomonas aeruginosa in human serum. Enzyme binds the four human plasma proteins, Factor H, factor H-like protein-1, complement factor H-related protein 1, and plasminogen. Factor H contacts the enzyme via short consensus repeats 7 and 18-20. Factor H, factor H-like protein-1, and plasminogen when bound to enzyme are functionally active. Bacterial survival is reduced when the enzyme is blocked on the surface prior to challenge with human serum. Similarly, bacterial survival is reduced up to 84% when the bacteria are challenged with complement active serum depleted of factor H, factor H-like protein-1, and complement factor H-related protein 1
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physiological function
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LPD is a useful biocatalyst for regenerating NAD+
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physiological function
Starkeyomyces koorchalomoides FDUS 0337
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the protein acetyltransferase activity of LADH can be attributed as a moonlighting function of the enzyme
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physiological function
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the enzyme is involved in adhesion to polystyrene as well as coelomocytes and other tissues like body wall, tentacle, muscle, respiratory tree and intestine from sea cucumber Apostichopus japonicas
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physiological function
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the enzyme shows titanium dioxide (TiO2) binding capability. The putative TiO2-binding regions of both the bacterial and human enzymes are found to contain a CHED (Cys, His, Glu, Asp) motif, which has been shown to participate in metal-binding sites in proteins. The binding of rhDLDH to TiO2 at physiological pH values and above is nonelectrostatic and involves chelating/coordinative interactions of DLDH acidic residues with the oxide, docking calculations
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physiological function
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LpdG, not LpdV and Lpd3, is the primary DLDH of the Pseudomonas aeruginosa PA14 pyruvate dehydrogenase, and is the enzymatically relevant DLDH for both pyruvate and 2-oxoglutarate dehydrogenase
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physiological function
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dihydrolipoamide dehydrogenase Lpd1 is a catalytic component of pyruvate dehydrogenase complex. LPD1 is required for filamentous growth under a serum-containing hyphal-inducing condition
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additional information
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a homology model for PfaE3 reveals an extra anti-parallel beta-strand at the position where human E3BP (E3-binding protein) interacts with E3, a parasite-specific feature that may be exploitable for drug discovery against PDC. E3 enzyme homology structure modelling using the human enzyme structure, PDB ID 2F5Z
additional information
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all of the E3 enzymes function as dimers, and their active site contains the reactive disulfide bridge, which is directly involved in catalysis
additional information
conformational change near the redox center of dihydrolipoamide dehydrogenase induced by NAD+ to regulate the enzyme activity
additional information
location of residue Cys50 in human E3 enzyme, structure comparisons with E3 enzymes from other species
additional information
location of residue H329 in human E3 enzyme, structure comparisons with E3 enzymes from other species
additional information
location of residues Pro156 and Pro303 in human E3 enzyme, structure comparisons with E3 enzymes from other species
additional information
mitochondrial lipoamide dehydrogenase is an important protein for determining the sensitivity of oxidative metabolism to arsenate in Arabidopsis thaliana
additional information
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mitochondrial lipoamide dehydrogenase is an important protein for determining the sensitivity of oxidative metabolism to arsenate in Arabidopsis thaliana
additional information
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molecular dynamics simulation the conformation of enzyme LADH that is proposed to be compatible with the reactive oxygen species (ROS) generation
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful. Structural analysis of LpdG, overview
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful. Structural analysis of LpdG, overview
additional information
purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful. Structural analysis of LpdG, overview
additional information
residue Ala328 is absolutely conserved, suggesting that it might be important for the structure and function of human E3. Ala328 is a component of alpha-helix 8 and is located near the presumed dihydrolipoamide binding channel. Ala328 is also located close to the active disulfide center between Cys45 and Cys50
additional information
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structure homology modeling of rhDLDH using the crystal structure of Mycobacterium tuberculosis DLDH, PDB 2A8X, chain A, as template
additional information
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structure homology modeling of rhDLDH using the crystal structure of Mycobacterium tuberculosis DLDH, PDB 2A8X, chain A, as template
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additional information
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purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful. Structural analysis of LpdG, overview
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additional information
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purification of an NADH:PCA or NADPH:PCA oxidoreductase, active with phenazine-1-carboxylic acid and other phenazines, from Pseudomonas aeruginosa cell lysate is not successful
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