Abstract:The de novo pyrimidine biosynthesis pathway is an important route due to the relevance of its products, its implications in health and its conservation among organisms. Here, we investigated the regulation by lysine acetylation of this pathway. To this aim, intracellular and extracellular metabolites of the route were quantified, revealing a possible blockage of the pathway by acetylation of the OPRTase enzyme (orotate phosphoribosyltransferase). Chemical acetylation of OPRTase by acetyl‐P involved a decrease … Show more
“…In our experiment, treatment of lumichrome resulted in the inhibitory effect on Congo-red binding in a concentration-dependent manner ( Figure 4j ). This observation is consistent with the reduced bacterial motility and biofilm formation in Δ pyrE mutant strain of Pseudomonas aeruginosa (PA01) (Niazy et al , 2022) and E. coli (Lozano-Terol et al , 2023). Additionally, inhibition of biofilm formation in E. coli was observed with a decrease in PyrE activity due to acetylation at lysine 26 and 103 position (Lozano-Terol et al , 2023).…”
In our pursuit of understanding the protein-metabolite interactome, we introduced PROMIS, a co-fractionation mass spectrometry (CF-MS) technique focusing on biosynthetic and regulatory processes. However, the challenge lies in distinguishing true interactors from coincidental co-elution when a metabolite co-fractionates with numerous proteins. To address this, we integrated two chromatographic techniques-size exclusion and ion exchange-to enhance the mapping of protein-metabolite interactions (PMIs) in Escherichia coli. This integration aims to refine the PMI network by considering size and charge characteristics, resulting in 994 interactions involving 51 metabolites and 465 proteins. The PMI network is enriched for known and predicted interactions validating our approach's efficacy. Furthermore, the analysis of protein targets for different metabolites revealed novel functional insights, such as the connection between proteinogenic dipeptides and fatty acid biosynthesis. Notably, we uncovered an inhibitory interaction between the riboflavin degradation product lumichrome and orotate phosphoribosyltransferase (PyrE), a key enzyme in de novo pyrimidine synthesis. Lumichrome supplementation mimicked the biofilm formation inhibition observed in a deltapyrE mutant strain, suggesting lumichrome role in integrating pyrimidine and riboflavin metabolism with quorum sensing and biofilm formation. In summary, our integrated chromatographic approach significantly advances PMI mapping, offering novel insights into functional associations and potential regulatory mechanisms in E. coli.
“…In our experiment, treatment of lumichrome resulted in the inhibitory effect on Congo-red binding in a concentration-dependent manner ( Figure 4j ). This observation is consistent with the reduced bacterial motility and biofilm formation in Δ pyrE mutant strain of Pseudomonas aeruginosa (PA01) (Niazy et al , 2022) and E. coli (Lozano-Terol et al , 2023). Additionally, inhibition of biofilm formation in E. coli was observed with a decrease in PyrE activity due to acetylation at lysine 26 and 103 position (Lozano-Terol et al , 2023).…”
In our pursuit of understanding the protein-metabolite interactome, we introduced PROMIS, a co-fractionation mass spectrometry (CF-MS) technique focusing on biosynthetic and regulatory processes. However, the challenge lies in distinguishing true interactors from coincidental co-elution when a metabolite co-fractionates with numerous proteins. To address this, we integrated two chromatographic techniques-size exclusion and ion exchange-to enhance the mapping of protein-metabolite interactions (PMIs) in Escherichia coli. This integration aims to refine the PMI network by considering size and charge characteristics, resulting in 994 interactions involving 51 metabolites and 465 proteins. The PMI network is enriched for known and predicted interactions validating our approach's efficacy. Furthermore, the analysis of protein targets for different metabolites revealed novel functional insights, such as the connection between proteinogenic dipeptides and fatty acid biosynthesis. Notably, we uncovered an inhibitory interaction between the riboflavin degradation product lumichrome and orotate phosphoribosyltransferase (PyrE), a key enzyme in de novo pyrimidine synthesis. Lumichrome supplementation mimicked the biofilm formation inhibition observed in a deltapyrE mutant strain, suggesting lumichrome role in integrating pyrimidine and riboflavin metabolism with quorum sensing and biofilm formation. In summary, our integrated chromatographic approach significantly advances PMI mapping, offering novel insights into functional associations and potential regulatory mechanisms in E. coli.
Pyrimidine biosynthesis and ribonucleoside metabolism in species of Pseudomonas was the focus of this review, in relation to their current taxonomic assignments in different homology groups. It was of interest to learn whether pyrimidine biosynthesis in taxonomically related species of Pseudomonas was regulated in a similar fashion by pyrimidine base supplementation or by pyrimidine limitation of pyrimidine auxotrophic strains. It was concluded that the regulation of pyrimidine biosynthesis in Pseudomonas species could not be correlated with their taxonomic assignment into a specific homology group. Pyrimidine ribonucleoside metabolism in Pseudomonas species primarily involved the pyrimidine ribonucleoside salvage enzymes nucleoside hydrolase and cytosine deaminase, independently of the Pseudomonas homology group to which the species was assigned. Similarly, pyrimidine base catabolism was shown to be active in different taxonomic homology groups of Pseudomonas. Although the number of studies exploring the catabolism of the pyrimidine bases uracil and thymine was limited in scope, it did appear that the presence of the pyrimidine base reductive pathway of pyrimidine catabolism was a commonality observed for the species of Pseudomonas investigated. There also appeared to be a connection between pyrimidine ribonucleoside degradation and the catabolism of pyrimidine bases in providing a cellular source of carbon or nitrogen independently of which homology group the species of Pseudomonas were assigned to.
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