Strategic allocation of metabolic flux is essential for achieving a higher production performance in genetically engineered organisms. Flux optimization between cell growth and chemical production has led to the establishment of cost-effective chemical production methods in microbial cell factories. This effect is amplified when utilizing a low-cost carbon source. γ-Aminobutyric acid (GABA), crucial in pharmaceuticals and biodegradable polymers, can be efficiently produced from acetate, a cost-effective substrate. However, a balanced distribution of acetate-derived flux is essential for optimizing the production without hindering growth. In this study, we demonstrated GABA production from acetate using Escherichia coli by focusing on optimizing the metabolic flux at isocitrate and α-ketoglutarate nodes. Through a series of flux optimizations, the final strain produced 2.54 g/L GABA from 5.91 g/L acetate in 24 h (0.43 g/g yield). These findings suggest that delicate flux balancing with the application of a cheap substrate can contribute to cost-effective production of GABA.

中文翻译：

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逐步通量优化以提高大肠杆菌中乙酸盐的 GABA 产量

代谢通量的战略分配对于基因工程生物体实现更高的生产性能至关重要。细胞生长和化学品生产之间的通量优化导致在微生物细胞工厂中建立了具有成本效益的化学品生产方法。当使用低成本碳源时，这种效应会被放大。 γ-氨基丁酸 (GABA) 在药物和可生物降解聚合物中至关重要，可以用醋酸盐（一种经济高效的底物）高效生产。然而，醋酸盐衍生通量的平衡分布对于在不阻碍生长的情况下优化生产至关重要。在这项研究中，我们通过重点优化异柠檬酸和 α-酮戊二酸节点的代谢通量，展示了使用大肠杆菌从乙酸盐生产 GABA。通过一系列通量优化，最终菌株在 24 小时内从 5.91 g/L 乙酸盐中产生了 2.54 g/L GABA（产量为 0.43 g/g）。这些发现表明，微妙的通量平衡与廉价底物的应用有助于以成本效益的方式生产 GABA。