Proton Nuclear Magnetic Resonance Metabolomics Corroborates Serine Hydroxymethyltransferase as the Primary Target of 2-Aminoacrylate in a ridA Mutant of Salmonella enterica

MSystems
Andrew J BorchertDiana M Downs

Abstract

The reactive intermediate deaminase RidA (EC 3.5.99.10) is conserved across all domains of life and deaminates reactive enamine species. When Salmonella entericaridA mutants are grown in minimal medium, 2-aminoacrylate (2AA) accumulates, damages several pyridoxal 5'-phosphate (PLP)-dependent enzymes, and elicits an observable growth defect. Genetic studies suggested that damage to serine hydroxymethyltransferase (GlyA), and the resultant depletion of 5,10-methelenetetrahydrofolate (5,10-mTHF), was responsible for the observed growth defect. However, the downstream metabolic consequence from GlyA damage by 2AA remains relatively unexplored. This study sought to use untargeted proton nuclear magnetic resonance (1H NMR) metabolomics to determine whether the metabolic state of an S. entericaridA mutant was accurately reflected by characterizing growth phenotypes. The data supported the conclusion that metabolic changes in a ridA mutant were due to the IlvA-dependent generation of 2AA, and that the majority of these changes were a consequence of damage to GlyA. While many of the metabolic differences for a ridA mutant could be explained, changes in some metabolites were not easily modeled, suggesting that additional levels of metabo...Continue Reading

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Citations

Nov 13, 2020·Analytical Chemistry·Arthur S EdisonSicong Zhang
Sep 5, 2021·Magnetic Resonance in Chemistry : MRC·Stefan KuhnRicardo Moreira Borges

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Methods Mentioned

BETA
deamination
nuclear magnetic resonance
dissect
PCA
NMR
dissection

Software Mentioned

Metabolomics Workbench
_ Toolbox Research
DA
PLS
MATLAB

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