Quinolinic acid degradation mediated by a unique qut cluster in Pigmentiphaga sp. YJ18

Abstract

Quinolinic acid (QA), a natural pyridine derivative produced through the kynurenine pathway in living organisms, is linked to various neurodegenerative diseases due to its neurotoxicity. Although some bacteria have been reported to degrade QA, the underlying molecular mechanisms remain incomplete. In this study, a unique qut cluster responsible for QA degradation is identified in Pigmentiphaga sp. YJ18. The strain YJ18 could degrade and utilize QA as the sole carbon source for growth. Strain YJ18 efficiently degrade 100 mg/L QA within 48 h at 30 °C, pH 7.0, and 1% NaCl. The gene-disruption results showed that qutE is involved in the initial step of QA degradation, while qutI mediate the conversion of 6-hydroxypicolinic acid (6HPA) to downstream metabolites. Furthermore, the degradation of QA is negatively regulated by the MarR family transcriptional regulator QutR, which shared 61.97% amino similarity with PicR in Alcaligenes faecalis. The qut gene cluster consists of three transcriptional units: qutABCDEF, qutGHIJKLMNO, and qutR. Electrophoretic mobility shift assay results demonstrated that QutR binds to the promoter regions of the qutA, qutG, and qutR, respectively, sharing a partial palindromic motif 5′-TCAG-N4-CTNN-3’. Bioinformatics analysis reveals that the unique qut cluster, co-evolving with Pigmentiphaga strains, integrating the qui and pic clusters which are responsible for degradation of QA to 6HPA and picolinic acid to fumaric acid, respectively. Overall, this study provides a newly isolated strain capable of degrading QA with a unique qut cluster and valuable molecular insights into the diversity of QA catabolic mechanisms in bacteria.