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.

中文翻译：

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综合的代谢组学和转录组学研究表明，沙门氏菌对2-氨基丙烯酸酯胁迫具有整体代谢反应。

在肠沙门氏菌中，2-氨基丙烯酸酯（2AA）是在许多生化反应过程中生成的一种反应性烯胺中间体。当2-亚氨基丁酸酯/ 2-亚氨基丙酸酯脱氨酶（RidA; EC：3.5.99.10）消除时，2AA会积累并抑制多种吡ido醛5'-磷酸（PLP）依赖性酶的活性。在这项研究中，未靶向的质子核磁共振（1H NMR）代谢组学和转录组学数据被用于揭示小肠链球菌对2AA积累的整体代谢反应。数据显示，消除RidA会扰乱叶酸和支链氨基酸的代谢。许多由此产生的扰动与2AA胁迫的已知作用是一致的，而其他结果则表明了2AA依赖性损伤的其他潜在酶靶标。转录和代谢变化的大部分似乎是下游对代谢网络影响的结果，因为它们并不直接归因于PLP依赖性酶。总的来说，这些结果突出了由代谢网络的多种扰动引起的变化的复杂性，并提出了一些假设，这些假设在未来对内源性2AA胁迫的RidA范式的研究中将是有价值的。