Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i>
In <i>Salmonella enterica</i>, 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 pyr...
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MDPI AG
2019-12-01
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| Series: | Metabolites |
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| Online Access: | https://www.mdpi.com/2218-1989/10/1/12 |
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| author | Andrew J. Borchert Jacquelyn M. Walejko Adrien Le Guennec Dustin C. Ernst Arthur S. Edison Diana M. Downs |
| author_facet | Andrew J. Borchert Jacquelyn M. Walejko Adrien Le Guennec Dustin C. Ernst Arthur S. Edison Diana M. Downs |
| author_sort | Andrew J. Borchert |
| collection | DOAJ |
| description | In <i>Salmonella enterica</i>, 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 (<sup>1</sup>H NMR) metabolomics and transcriptomics data were used to uncover the global metabolic response of <i>S. enterica</i> 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. |
| first_indexed | 2024-12-10T21:45:58Z |
| format | Article |
| id | doaj.art-a715b7ba2164471b8ff1bcda125798d3 |
| institution | Directory Open Access Journal |
| issn | 2218-1989 |
| language | English |
| last_indexed | 2024-12-10T21:45:58Z |
| publishDate | 2019-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Metabolites |
| spelling | doaj.art-a715b7ba2164471b8ff1bcda125798d32022-12-22T01:32:22ZengMDPI AGMetabolites2218-19892019-12-011011210.3390/metabo10010012metabo10010012Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i>Andrew J. Borchert0Jacquelyn M. Walejko1Adrien Le Guennec2Dustin C. Ernst3Arthur S. Edison4Diana M. Downs5Department of Microbiology, University of Georgia, Athens, GA 30602, USADepartment of Biochemistry & Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USADepartment of Biochemistry & Molecular Biology, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USADepartment of Microbiology, University of Georgia, Athens, GA 30602, USADepartments of Genetics and Biochemistry & Molecular Biology, Institute of Bioinformatics, Complex Carbohydrate Research Center, University of Georgia, Athens, GA 30602, USADepartment of Microbiology, University of Georgia, Athens, GA 30602, USAIn <i>Salmonella enterica</i>, 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 (<sup>1</sup>H NMR) metabolomics and transcriptomics data were used to uncover the global metabolic response of <i>S. enterica</i> 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.https://www.mdpi.com/2218-1989/10/1/122-aminoacrylate stressridapyridoxal 5′-phosphatemetabolic networksmetabolomics<sup>1</sup>h nmr |
| spellingShingle | Andrew J. Borchert Jacquelyn M. Walejko Adrien Le Guennec Dustin C. Ernst Arthur S. Edison Diana M. Downs Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> Metabolites 2-aminoacrylate stress rida pyridoxal 5′-phosphate metabolic networks metabolomics <sup>1</sup>h nmr |
| title | Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> |
| title_full | Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> |
| title_fullStr | Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> |
| title_full_unstemmed | Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> |
| title_short | Integrated Metabolomics and Transcriptomics Suggest the Global Metabolic Response to 2-Aminoacrylate Stress in <i>Salmonella enterica</i> |
| title_sort | integrated metabolomics and transcriptomics suggest the global metabolic response to 2 aminoacrylate stress in i salmonella enterica i |
| topic | 2-aminoacrylate stress rida pyridoxal 5′-phosphate metabolic networks metabolomics <sup>1</sup>h nmr |
| url | https://www.mdpi.com/2218-1989/10/1/12 |
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