16662-90-1

Upstream product

• 52119-39-8 ethyl (2-nitrobenzoyl)acetate 
• 22751-16-2 2-nitrobenzoylacetic acid 

Downstream Products

• 2503-80-2 4-hydroxy-2-heptylquinoline 
• 341-88-8 2 heptyl 4 hydroxyquinoline 1 oxide 
• 40522-46-1 2-heptyl-quinolin-4(1H)-one 
• 70254-43-2 4-Hydroxy-2-quinolone 

Relevant academic research and scientific papers

Quinolactacin Biosynthesis Involves Non-Ribosomal-Peptide-Synthetase-Catalyzed Dieckmann Condensation to Form the Quinolone-γ-lactam Hybrid

Quinolactacins are novel fungal alkaloids that feature a quinolone-γ-lactam hybrid, which is a potential pharmacophore for the treatment of cancer and Alzheimer's disease. Herein, we report the identification of the quinolactacin A2 biosynthetic gene cluster and elucidate the enzymatic basis for the formation of the quinolone-γ-lactam structure. We reveal an unusual β-keto acid (N-methyl-2-aminobenzoylacetate) precursor that is derived from the primary metabolite l-kynurenine via methylation, oxidative decarboxylation, and amide hydrolysis reactions. In vitro assays reveal two single-module non-ribosomal peptide synthetases (NRPs) that incorporate the β-keto acid and l-isoleucine, followed by Dieckmann condensation, to form the quinolone-γ-lactam. Notably, the bioconversion from l-kynurenine to the β-keto acid is a unique strategy employed by nature to decouple R*-domain-containing NRPS from the polyketide synthase (PKS) machinery, expanding the paradigm for the biosynthesis of quinolone-γ-lactam natural products via Dieckmann condensation.

The end of an old hypothesis: The pseudomonas signaling molecules 4-hydroxy-2-alkylquinolines derive from fatty acids, not 3-ketofatty acids

Summary Groups of pathogenic bacteria use diffusible signals to regulate their virulence in a concerted manner. Pseudomonas aeruginosa uses 4-hydroxy-2-alkylquinolines (HAQs), including 4-hydroxy-2-heptylquinoline (HHQ) and 3,4-dihydroxy-2-heptylquinoline

Competitive Live-Cell Profiling Strategy for Discovering Inhibitors of the Quinolone Biosynthesis of Pseudomonas aeruginosa

Quinolones of the human pathogenPseudomonas aeruginosaserve as antibacterial weapons and quorum sensing signals and coordinate the production of important virulence factors. A central enzyme for the biosynthesis of these quinolones is the synthetase PqsD.

PqsL uses reduced flavin to produce 2-hydroxylaminobenzoylacetate, a preferred PqsBC substrate in alkyl quinolone biosynthesis in Pseudomonas aeruginosa

Alkyl hydroxyquinoline N-oxides (AQNOs) are antibiotic compounds produced by the opportunistic bacterial pathogen Pseudomonas aeruginosa. They are products of the alkyl quinolone (AQ) biosynthetic pathway, which also generates the quorum-sensing molecules 2-heptyl-4(1H)-quinolone (HHQ) and 2-heptyl-3-hydroxy-4(1H)-quinolone (PQS). Although the enzymatic synthesis of HHQ and PQS had been elucidated, the route by which AQNOs are synthesized remained elusive. Here, we report on PqsL, the key enzyme for AQNO production, which structurally resembles class A flavoprotein monooxygenases such as p-hydroxybenzoate 3-hydroxylase (pHBH) and 3-hydroxybenzoate 6-hydroxylase. However, we found that unlike related enzymes, PqsL hydroxylates a primary aromatic amine group, and it does not use NAD(P)H as cosubstrate, but unexpectedly required reduced flavin as electron donor. We also observed that PqsL is active toward 2-aminobenzoylacetate (2-ABA), the central intermediate of the AQ pathway, and forms the unstable compound 2-hydroxylaminobenzoylacetate, which was preferred over 2-ABA as substrate of the downstream enzyme PqsBC. In vitro reconstitution of the PqsL/PqsBC reaction was feasible by using the FAD reductase HpaC, and we noted that the AQ:AQNO ratio is increased in an hpaC-deletion mutant of P. aeruginosa PAO1 compared with the ratio in the WT strain. A structural comparison with pHBH, the model enzyme of class A flavoprotein monooxygenases, revealed that structural features associated with NAD(P)H binding are missing in PqsL. Our study completes the AQNO biosynthetic pathway in P. aeruginosa, indicating that PqsL produces the unstable product 2-hydroxylaminobenzoylacetate from 2-ABA and depends on free reduced flavin as electron donor instead of NAD(P)H.