Abstract
In Salmonella enterica, 2-aminoacrylate (2AA) is a reactive enamine intermediate generated during a number of biochemical reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA; EC: 3.5.99.10) is eliminated, 2AA accumulates and inhibits the activity of multiple pyridoxal 5’-phosphate(PLP)-dependent enzymes. In this study, untargeted proton nuclear magnetic resonance (1H NMR) metabolomics and transcriptomics data were used to uncover the global metabolic response of S. enterica to the accumulation of 2AA. The data showed that elimination of RidA perturbed folate and branched chain amino acid metabolism. Many of the resulting perturbations were consistent with the known effect of 2AA stress, while other results suggested additional potential enzyme targets of 2AA-dependent damage. The majority of transcriptional and metabolic changes appeared to be the consequence of downstream effects on the metabolic network, since they were not directly attributable to a PLP-dependent enzyme. In total, the results highlighted the complexity of changes stemming from multiple perturbations of the metabolic network, and suggested hypotheses that will be valuable in future studies of the RidA paradigm of endogenous 2AA stress.
Highlights
The metabolic network of an organism consists of a complex system of biochemical reactions that together result in the behavioral characteristics of the organism
Metabolite Levels Are Altered in an S. enterica reactions. When the 2-iminobutanoate/2-iminopropanoate deaminase (RidA) Mutant
Enterica LT2 strains that differed only at the ridA locus (DM9404 and DM3480) after growth to stationary phase in minimal glucose medium. These data were viewed through a biological lens, considering the role PLP-enzyme-dependent enzymes have in the ridA paradigm [29,30], to extract insights into the effect of 2AA stress on the metabolic network that goes beyond information gleaned from past genetic, biochemical, and transcriptomic analyses
Summary
The metabolic network of an organism consists of a complex system of biochemical reactions that together result in the behavioral characteristics of the organism. Technological advances continue to expand and to provide deeper and more detailed detailed global snapshots in a cell As or population. As these accumulate, large datasets accumulate, snapshots of features in a of cellfeatures or population. RidA paradigm of enamine in Salmonella enterica defines a metabolic scale. RidA of enamine stress stress in Salmonella enterica defines a metabolic modelmodel with with clearly defined local effects that in result in predictable global consequences. RidA protein responsible for the hydrolysis of enamine/imine species,species, which which are generated as intermediates in a of variety of biochemical [15,16,17,18,19,20] 1).
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have