Information on EC 2.3.1.230 - 2-heptyl-4(1H)-quinolone synthase

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The expected taxonomic range for this enzyme is: Pseudomonas aeruginosa

EC NUMBER
COMMENTARY hide
2.3.1.230
-
RECOMMENDED NAME
GeneOntology No.
2-heptyl-4(1H)-quinolone synthase
-
REACTION
REACTION DIAGRAM
COMMENTARY hide
ORGANISM
UNIPROT
LITERATURE
3-oxodecanoate + anthraniloyl-CoA = CoA + 2-heptyl-4(1H)-quinolone + CO2 + H2O
show the reaction diagram
(1)
-
-
-
malonyl-CoA + anthraniloyl-CoA = 2 CoA + 4-hydroxy-2(1H)-quinolone + CO2
show the reaction diagram
(2)
-
-
-
SYSTEMATIC NAME
IUBMB Comments
malonyl-CoA:anthraniloyl-CoA C-acetyltransferase (decarboxylating)
The enzyme from the Gram-negative bacterium Pseudomonas aeruginosa is involved in the biosynthesis of 2-heptyl-4-hydroxyquinoline and 2,4-dihydroxyquinoline. 2-Heptyl-4-hydroxyquinoline is a signal molecule, that is involved in regulation of virulence factor production and biofilm formation. The enzyme shows a broad specificity and is involved in the synthesis of a wide array of additional 2-alkyl-4(1H)-quinolones synthesized by the organism.
ORGANISM
COMMENTARY hide
LITERATURE
UNIPROT
SEQUENCE DB
SOURCE
cf. EC 2.3.1.180
UniProt
Manually annotated by BRENDA team
GENERAL INFORMATION
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
physiological function
SUBSTRATE
PRODUCT                       
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
Reversibility
r=reversible
ir=irreversible
?=not specified
3-oxodecanoate + 2-aminobenzoyl-CoA
CoA + 2-heptyl-4(1H)-quinolone + CO2 + H2O
show the reaction diagram
-
-
-
-
?
3-oxodecanoate + 2-aminobenzoyl-CoA
CoA + 2-heptyl-4-hydroxyquinoline + CO2 + H2O
show the reaction diagram
-
-
-
-
?
3-oxodecanoyl-CoA + 2-aminobenzoyl-CoA
2 CoA + 2-heptyl-3-hydroxy-4(1H)-quinolone + CO2
show the reaction diagram
-
high concentrations and a longer incubation time is required in comparison to the free 3-oxodecanoic acid
-
-
?
3-oxodecanoyl-N-acetylcysteamine + 2-aminobenzoyl-CoA
N-acetylcysteamine + 2-heptyl-3-hydroxy-4(1H)-quinolone + CO2
show the reaction diagram
-
high concentrations and a longer incubation time is required in comparison to the free 3-oxodecanoic acid
-
-
?
3-oxohexanoate + 2-aminobenzoyl-CoA
CoA + 2-propyl-4(1H)-quinolone + CO2 + H2O
show the reaction diagram
-
-
-
-
?
3-oxopentanoate + 2-aminobenzoyl-CoA
CoA + 2-ethyl-4(1H)-quinolone + CO2 + H2O
show the reaction diagram
-
-
-
-
?
malonyl-CoA + 2-aminobenzoyl-CoA
2 CoA + 4-hydroxy-2(1H)-quinolone + CO2
show the reaction diagram
malonyl-[acyl-carrier protein] + 2-aminobenzoyl-CoA
CoA + acyl-carrier protein + 4-hydroxy-2(1H)-quinolone + CO2
show the reaction diagram
-
first, the 2-aminobenzoyl moiety is transferred to the active-site Cys of PqsD to form a 2-aminobenzoyl-PqsD intermediate, which then condenses with either malonyl-CoA or malonyl-acyl carrier protein to produce 3-(2-aminophenyl)-3-oxopropanoyl-CoA. This short-lived intermediate undergoes an intramolecular rearrangement to form 2,4-dihydroxyquinoline
i.e. 2,4-dihydroxyquinoline
-
?
additional information
?
-
-
no activity with malonic acid or 2-hydroxybenzoate
-
-
-
NATURAL SUBSTRATES
NATURAL PRODUCTS
REACTION DIAGRAM
ORGANISM
UNIPROT
COMMENTARY
(Substrate) hide
LITERATURE
(Substrate)
COMMENTARY
(Product) hide
LITERATURE
(Product)
REVERSIBILITY
r=reversible
ir=irreversible
?=not specified
malonyl-CoA + 2-aminobenzoyl-CoA
2 CoA + 4-hydroxy-2(1H)-quinolone + CO2
show the reaction diagram
INHIBITORS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
(2-nitrophenyl)(phenyl)methanol
-
0.05 mM, 99% inhibition
(2-nitrophenyl)(thiophen-3-yl)methanol
-
inhibitor shows almost no time-dependency of PqsD inhibition
(2R)-2,4-dihydroxy-3,3-dimethyl-N-(3-[[4-(2-nitrophenyl)-4-oxobutyl]amino]-3-oxopropyl)butanamide
-
0.05 mM, 18% inhibition
(2R)-2,4-dihydroxy-N-(3-[[4-hydroxy-4-(2-nitrophenyl)butyl]amino]-3-oxopropyl)-3,3-dimethylbutanamide
-
0.05 mM, 95% inhibition
(S)-(2-nitrophenyl)(phenyl)methanol
-
most active compound of the series, capable of reducing the HHQ and PQS levels as well as the biofilm volume in Pseudomonas aeruginosa PA14 without affecting cell viability. The (S)-enantiomer has a pronounced entropic binding profile. Docking results show a short hydrogen bond between NO2 and NH of Ser317. The hydroxyl group is involved in different interactions, either facing toward Asn287 or His256/Cys112
-
1-(2-nitrophenyl)propan-1-ol
-
best inhibitor in the cellular test
1-benzyl-2-nitrobenzene
-
0.025 mM, 24% inhibition
1-[methoxy(phenyl)methyl]-2-nitrobenzene
-
0.05 mM, 97% inhibition
2-(4-bromo-3-diethylsulfamoylbenzoylamino)benzoate
-
-
2-([3-[benzyl(ethyl)sulfamoyl]benzoyl]amino)benzoic acid
-
-
2-chloro-6-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
2-nitrophenyl phenyl sulfone
-
0.05 mM, 87% inhibition
2-[(2-phenoxybiphenyl-4-carbonyl)amino]benzoate
-
-
2-[(3-sulfamoylbenzoyl)amino]benzoic acid
-
-
2-[[3-(azepan-1-ylsulfonyl)benzoyl]amino]benzoic acid
-
-
2-[[3-(diethylsulfamoyl)-4-ethylbenzoyl]amino]benzoic acid
-
0.05 mM, 39% inhibition
2-[[3-(diethylsulfamoyl)-4-methylbenzoyl]amino]benzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-4-fluorobenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-4-nitrobenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-(trifluoromethyl)benzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-fluorobenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-methylbenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-nitrobenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-6-fluorobenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-6-hydroxybenzoic acid
-
-
2-[[3-(diethylsulfamoyl)benzoyl]amino]-6-methoxybenzoic acid
-
0.05 mM, 44% inhibition
2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
2-[[3-(dimethylsulfamoyl)benzoyl]amino]benzoic acid
-
0.05 mM, 35% inhibition
2-[[3-(dipropylsulfamoyl)benzoyl]amino]benzoic acid
-
-
2-[[3-(morpholin-4-ylsulfonyl)benzoyl]amino]benzoic acid
-
0.05 mM, 16% inhibition
2-[[3-(piperidin-1-ylsulfonyl)benzoyl]amino]benzoic acid
-
-
2-[[3-(pyrrolidin-1-ylsulfonyl)benzoyl]amino]benzoic acid
-
0.05 mM, 47% inhibition
2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]-5-fluorobenzoic acid
-
-
2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
3'-carbamoyl-4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
-
-
3-(3,4-dihydroxyphenyl)-N-methylpropanamide
-
potent inhibitor, completely inactive in the cell-based assay
4'-carbamoyl-4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
-
-
4-chloro-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3,3'-dicarboxylic acid
-
-
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3,4'-dicarboxylic acid
-
-
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
-
-
5-bromo-2-[[3-(diethylcarbamoyl)benzoyl]amino]benzoic acid
-
-
5-bromo-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
5-bromo-2-[[4-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
5-bromo-2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
5-cyano-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
-
-
benzyl 3-(3,4-dihydroxyphenyl)propanoate
-
-
methyl 3-(3,4-dihydroxyphenyl)propanoate
-
potent inhibitor
N-(2-chloro-6-methylphenyl)biphenyl-4-carboxamide
-
strong inhibition of enzyme, without inhibition of RNA polymerase
N-[2-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
-
0.05 mM, 93% inhibition
N-[3-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
-
0.05 mM, 99% inhibition
N-[4-(2-nitrophenyl)-4-oxobutyl]acetamide
-
0.05 mM, 98% inhibition
N-[4-hydroxy-4-(2-nitrophenyl)butyl]acetamide
-
0.05 mM, 99% inhibition
N-[4-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
-
0.05 mM, 98% inhibition
additional information
-
KM VALUE [mM]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.035 - 0.875
2-aminobenzoyl-CoA
1.3
3-oxodecanoate
-
pH 7, 37°C
0.0487 - 0.104
malonyl-CoA
0.018
malonyl-[acyl-carrier protein]
-
pH 7.5, 37°C
TURNOVER NUMBER [1/s]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.0165
2-aminobenzoyl-CoA
kcat/KM VALUE [1/mMs-1]
SUBSTRATE
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
0.014
2-aminobenzoyl-CoA
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
3586
69
malonyl-CoA
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
76
IC50 VALUE [mM]
INHIBITOR
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
IMAGE
3.2
(2-nitrophenyl)(phenyl)methanol
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0059
(2-nitrophenyl)(thiophen-3-yl)methanol
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
7.9
(2R)-2,4-dihydroxy-N-(3-[[4-hydroxy-4-(2-nitrophenyl)butyl]amino]-3-oxopropyl)-3,3-dimethylbutanamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0032
(S)-(2-nitrophenyl)(phenyl)methanol
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
-
0.0011
1-(2-nitrophenyl)propan-1-ol
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
4.3
1-[methoxy(phenyl)methyl]-2-nitrobenzene
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.065
2-(4-bromo-3-diethylsulfamoylbenzoylamino)benzoate
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0165
2-([3-[benzyl(ethyl)sulfamoyl]benzoyl]amino)benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.039
2-chloro-6-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
14.8
2-nitrophenyl phenyl sulfone
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.035
2-[(2-phenoxybiphenyl-4-carbonyl)amino]benzoate
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.044
2-[(3-sulfamoylbenzoyl)amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0148
2-[[3-(azepan-1-ylsulfonyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0273
2-[[3-(diethylsulfamoyl)-4-methylbenzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.008
2-[[3-(diethylsulfamoyl)benzoyl]amino]-4-fluorobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0063
2-[[3-(diethylsulfamoyl)benzoyl]amino]-4-nitrobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0124
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-(trifluoromethyl)benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0114
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-fluorobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0184
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-methylbenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0089
2-[[3-(diethylsulfamoyl)benzoyl]amino]-5-nitrobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.025
2-[[3-(diethylsulfamoyl)benzoyl]amino]-6-fluorobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0012
2-[[3-(diethylsulfamoyl)benzoyl]amino]-6-hydroxybenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0198
2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0054
2-[[3-(dipropylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0144
2-[[3-(piperidin-1-ylsulfonyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0066
2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]-5-fluorobenzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0069
2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0038
3'-carbamoyl-4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.023
3-(3,4-dihydroxyphenyl)-N-methylpropanamide
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
0.0019
4'-carbamoyl-4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0094
4-chloro-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0015
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3,3'-dicarboxylic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0027
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3,4'-dicarboxylic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.003
4-[[3-(diethylsulfamoyl)benzoyl]amino]biphenyl-3-carboxylic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0255
5-bromo-2-[[3-(diethylcarbamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.009
5-bromo-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.013
5-bromo-2-[[4-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0038
5-bromo-2-[[4-bromo-3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.026
5-cyano-2-[[3-(diethylsulfamoyl)benzoyl]amino]benzoic acid
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
0.0059
benzyl 3-(3,4-dihydroxyphenyl)propanoate
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
0.02
methyl 3-(3,4-dihydroxyphenyl)propanoate
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
0.0062
N-(2-chloro-6-methylphenyl)biphenyl-4-carboxamide
Pseudomonas aeruginosa
-
pH not specified in the publication, temperature not specified in the publication
6.2
N-[2-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
9
N-[3-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
7.8
N-[4-(2-nitrophenyl)-4-oxobutyl]acetamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
4.3
N-[4-hydroxy-4-(2-nitrophenyl)butyl]acetamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
6.4
N-[4-[hydroxy(2-nitrophenyl)methyl]phenyl]acetamide
Pseudomonas aeruginosa
-
pH and temperature not specified in the publication
SPECIFIC ACTIVITY [µmol/min/mg]
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
0.22
-
pH 7.5, 37°C
pH OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
TEMPERATURE OPTIMUM
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
PDB
SCOP
CATH
ORGANISM
UNIPROT
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
Pseudomonas aeruginosa (strain ATCC 15692 / PAO1 / 1C / PRS 101 / LMG 12228)
MOLECULAR WEIGHT
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
38440
-
HPLC mass spectrometry
72800
-
gel filtration, laser light scattering
SUBUNITS
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
homodimer
-
2 * 36000
Crystallization/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
molecular dynamics simulations suggest a nucleophilic attack of the deprotonated sulfur of Cys112 at the carbonyl carbon of ACoA and a switch in the protonation pattern of His257 whereby Ndelta is protonated and the proton of Nepsilon is shifted to the sulfur of CoA during the reaction. In the N287A mutant anthraniloyl remains covalently bound to C112, further supporting that N87 does not take part in the cleavage of anthraniloyl-CoA
-
sitting drop vapor diffusion method. Several crystal structures of the enzyme including that of the PqsD-anthranilate covalent intermediate and the inactive Cys112Ala active site mutant in complex with anthranilate
-
Purification/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
Cloned/COMMENTARY
ORGANISM
UNIPROT
LITERATURE
4-hydroxy-2(1H)-quinolone is produced by Escherichia coli coexpressing PqsA and PqsD
-
expression in Escherichia coli
-
overexpression in Escherichia coli
-
ENGINEERING
ORGANISM
UNIPROT
COMMENTARY hide
LITERATURE
N287A
-
inactive, anthraniloyl remains covalently bound to C112, further supporting that N87 does not take part in the cleavage of anthraniloyl-CoA
S317A
-
activity similar to wild-type