Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in Salmonella enterica
by
Andrew J. Borchert 1,†, Jacquelyn M. Walejko 2,‡, Adrien Le Guennec 2,§, Dustin C. Ernst 1,‖, Arthur S. Edison 3
and Diana M. Downs 1,*
Andrew J. Borchert 1,†, Jacquelyn M. Walejko 2,‡, Adrien Le Guennec 2,§, Dustin C. Ernst 1,‖, Arthur S. Edison 3 and Diana M. Downs 1,*
1
Department of Microbiology, University of Georgia, Athens, GA 30602, USA
2
Department of Biochemistry & Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
3
Departments of Genetics and Biochemistry & Molecular Biology, Institute of Bioinformatics, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USA
*
Author to whom correspondence should be addressed.
†
Current Address: National Bioenergy Center, National Renewable Energy Laboratory, Golden, CO 90401, USA.
‡
Current Address: Duke Molecular Physiology Institute, Duke University, Durham, NC 27701, USA.
§
Current Address: Centre for Biomolecular Spectroscopy and Randal Division of Cell and Molecular Biophysics, King’s College London, New Hunt’s House, London SE1 1UL, UK.
‖
Current Address: Center for Circadian Biology, University of California, San Diego, CA 92161, USA.
Metabolites 2020, 10(1), 12; https://doi.org/10.3390/metabo10010012
Received: 15 November 2019 / Revised: 19 December 2019 / Accepted: 20 December 2019 / Published: 24 December 2019
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.
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Keywords:
2-aminoacrylate stress; RidA; pyridoxal 5′-phosphate; metabolic networks; metabolomics; 1H NMR
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MDPI and ACS Style
Borchert, A.J.; Walejko, J.M.; Guennec, A.L.; Ernst, D.C.; Edison, A.S.; Downs, D.M. Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in Salmonella enterica. Metabolites 2020, 10, 12.
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