L-2,3-diaminopropionate generates diverse metabolic stresses in Salmonella enterica.
L-2,3-diaminopropionate generates diverse metabolic stresses in Salmonella enterica.
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DOI：
10.1111/mmi.13384
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发表时间：
2016-07
影响因子：
3.6
通讯作者：
Downs DM
中科院分区：
文献类型：
--
作者：
Ernst DC;Anderson ME;Downs DM
活细胞中不受控制的氨基酸积累有可能通过破坏正常的代谢过程而引起压力。因此，许多生物体已经进化出防止氨基酸内源积累的降解策略。L-2，3-二氨基丙酸（Dap）是一种非蛋白质氨基酸，在自然界中作为铁载体，神经毒素和抗生素的前体。S.先前显示肠毒素通过未知的机制抑制生长。二氨基丙酸解氨酶（DpaL）的产生减轻了S.肠杆菌通过催化Dap降解为丙酮酸和氨。在这里，我们证明了Dap积累在S。肠杆菌（enterica elastica）是生长所需的脯氨酸，并且特异性地抑制辅酶A和异亮氨酸生物合成。此外，我们确定Dap至丙酮酸的DpaL依赖性降解通过未结合的2-氨基丙烯酸酯（2AA）中间体进行，从而导致细胞内的2AA应激。反应性中间体脱氨酶RidA通过提高2AA水解速率来防止由DpaL依赖性Dap降解引起的2AA损伤。本文提供的结果告知我们的理解Dap对代谢的影响在S。enterica和可能的其他生物，并强调了RidA在预防源于Dap解毒的2AA应激中发挥的关键作用。
Unchecked amino acid accumulation in living cells has the potential to cause stress by disrupting normal metabolic processes. Thus, many organisms have evolved degradation strategies that prevent endogenous accumulation of amino acids. L-2,3-diaminopropionate (Dap) is a non-protein amino acid produced in nature where it serves as a precursor to siderophores, neurotoxins, and antibiotics. Dap accumulation in S. enterica was previously shown to inhibit growth by unknown mechanisms. The production of diaminopropionate ammonia-lyase (DpaL) alleviated Dap toxicity in S. enterica by catalyzing the degradation of Dap to pyruvate and ammonia. Here, we demonstrate that Dap accumulation in S. enterica elicits a proline requirement for growth and specifically inhibits coenzyme A and isoleucine biosynthesis. Additionally, we establish that the DpaL-dependent degradation of Dap to pyruvate proceeds through an unbound 2-aminoacrylate (2AA) intermediate, thus contributing to 2AA stress inside the cell. The reactive intermediate deaminase, RidA, is shown to prevent 2AA damage caused by DpaL-dependent Dap degradation by enhancing the rate of 2AA hydrolysis. The results presented herein inform our understanding of the effects Dap has on metabolism in S. enterica, and likely other organisms, and highlight the critical role played by RidA in preventing 2AA stress stemming from Dap detoxification.