Maintaining a delicate balance of adenosine-5′-triphosphate (ATP) is crucial not only for optimal cellular functions but also for improved metabolite production, indicating the need for careful regulation of ATP demands in metabolic engineering. This study explored the modification of ATP metabolism to enhance adipic acid production in Escherichia coli, focusing on the reverse adipate degradation pathway (RADP), and ATP-consuming cycles were fine-tuned by controlling the overexpression of genes (panK and acs) to balance ATP consumption and adipic acid production. As a result, we successfully achieved a significant increase (19.5-fold) in adipic acid production, reaching 1093.11 mg/L in a shake flask, compared to that in the control strain (wild-type E. coli harboring the RADP). Our transcriptomic analysis indicated that modulation of ATP metabolism, along with a balanced supply of pathway precursors, affects metabolic fluxes, enhancing adipic acid biosynthesis in E. coli. This study suggests the potential of metabolic reprogramming of ATP to meet biosynthetic demands, which may improve the production of adipic acid and other ATP-derived chemicals.

中文翻译：

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ATP 代谢的协调重编程强烈增强了大肠杆菌中己二酸的产生


维持腺苷-5′-三磷酸 （ATP） 的微妙平衡不仅对最佳细胞功能至关重要，而且对改善代谢物产生也至关重要，这表明在代谢工程中需要仔细调节 ATP 需求。本研究探讨了 ATP 代谢的修饰以增强大肠杆菌中己二酸的产生，重点是反向己二酸降解途径 （RADP），并通过控制基因 （panK 和 acs） 的过表达来微调 ATP 消耗周期以平衡 ATP 消耗和己二酸的产生。结果，与对照菌株（含有 RADP 的野生型大肠杆菌）相比，我们成功地实现了己二酸产量的显著增加（19.5 倍），在摇瓶中达到 1093.11 mg/L。我们的转录组学分析表明，ATP 代谢的调节以及途径前体的平衡供应会影响代谢通量，增强大肠杆菌中的己二酸生物合成。这项研究表明 ATP 的代谢重编程有可能满足生物合成需求，这可能会改善己二酸和其他 ATP 衍生化学物质的产生。