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Literature summary for 2.3.1.B38 extracted from

  • Allegretta, G.; Maurer, C.; Eberhard, J.; Maura, D.; Hartmann, R.; Rahme, L.; Empting, M.
    In-depth profiling of MvfR-regulated small molecules in Pseudomonas aeruginosa after Quorum Sensing inhibitor treatment (2017), Front. Microbiol., 8, 924 .
    View publication on PubMedView publication on EuropePMC

Protein Variants

Protein Variants Comment Organism
additional information Pseudomonas aeruginosa strain PA14 isogenic transposon pqsC mutant Pseudomonas aeruginosa

Inhibitors

Inhibitors Comment Organism Structure
(furan-3-yl)(2-nitrophenyl)methanol PqsBC inhibitor reduces the production of the MvfR natural ligands in wild-type strain PA14 down to 34% at its highest concentration Pseudomonas aeruginosa
ethyl 3-benzyl-1-[2-(4-fluoroanilino)-2-oxoethyl]-2,4-dioxo-1,3,4,5,6,8-hexahydropyrido[4',3':4,5]thieno[2,3-d]pyrimidine-7(2H)-carboxylate PqsBC inhibitor reduces the production of the MvfR natural ligands in wild-type strain PA14 down to 35% at its highest concentration Pseudomonas aeruginosa
additional information Pseudomonas aeruginosa is a Gram-negative bacterium, which causes opportunistic infections in immuno-compromised individuals. Due to its multiple resistances toward antibiotics, the development of new drugs is required. Interfering with quorum sensing (QS), a cell-to-cell communication system, has shown to be highly efficient in reducing Pseudomonas aeruginosa pathogenicity. One of its QS systems employs Pseudomonas quinolone signal (PQS) and 4-hydroxy-2-heptylquinoline (HHQ) as signal molecules. Both activate the transcriptional regulator MvfR (Multiple Virulence Factor Regulator), also called PqsR, driving the production of QS molecules as well as toxins and biofilm formation. Effects of QS inhibitors (QSIs), such as MvfR antagonists and PqsBC inhibitors, on the biosynthesis of the MvfR-regulated small molecules 2'-aminoacetophenone (2-AA), dihydroxyquinoline (DHQ), 4-hydroxy-2-heptylquinoline (HHQ), Pseudomonas quinolone signal (PQS), and 4-hydroxy-2-heptylquinoline-N-oxide (HQNO). The employed synthetic MvfR antagonist fully inhibits pqs small molecule formation showing expected sigmoidal dose-response curves for 2-AA, HQNO, HHQ, and PQS Pseudomonas aeruginosa

Natural Substrates/ Products (Substrates)

Natural Substrates Organism Comment (Nat. Sub.) Natural Products Comment (Nat. Pro.) Rev. Reac.
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa ATCC 15692
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa 1C
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa PRS 101
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa DSM 22644
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa CIP 104116
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa LMG 12228
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate Pseudomonas aeruginosa JCM 14847
-
2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?

Organism

Organism UniProt Comment Textmining
Pseudomonas aeruginosa Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa 1C Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa ATCC 15692 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa CIP 104116 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa DSM 22644 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa JCM 14847 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa LMG 12228 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-
Pseudomonas aeruginosa PRS 101 Q9I4X1 AND Q9I4X2 2-heptyl-4(1H)-quinolone synthase subunits PqsC and PqsB
-

Substrates and Products (Substrate)

Substrates Comment Substrates Organism Products Comment (Products) Rev. Reac.
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa ATCC 15692 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa 1C 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa PRS 101 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa DSM 22644 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa CIP 104116 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa LMG 12228 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?
octanoyl-CoA + (2-aminobenzoyl)acetate
-
Pseudomonas aeruginosa JCM 14847 2-heptyl-4-quinolone + CoA + CO2 + H2O
-
?

Synonyms

Synonyms Comment Organism
2-heptyl-4(1H)-quinolone synthase
-
Pseudomonas aeruginosa
PqsB
-
Pseudomonas aeruginosa
PqsBC
-
Pseudomonas aeruginosa
PqsC
-
Pseudomonas aeruginosa

General Information

General Information Comment Organism
malfunction effects of QS inhibitors (QSIs), such as MvfR antagonists and PqsBC inhibitors, on the biosynthesis of the MvfR-regulated small molecules 2'-aminoacetophenone (2-AA), dihydroxyquinoline (DHQ), 4-hydroxy-2-heptylquinoline (HHQ), Pseudomonas quinolone signal (PQS), and 4-hydroxy-2-heptylquinoline-N-oxide (HQNO) Pseudomonas aeruginosa
metabolism the 2-heptyl-4(1H)-quinolone synthase is involved in the biosynthetic pathway of MvfR-related small molecules. In-depth profiling of MvfR-regulated small molecules in Pseudomonas aeruginosa after quorum sensing inhibitor treatment Pseudomonas aeruginosa