The trade-offs exist between microbial growth and bioproduct synthesis including intracellular polyester polyhydroxybutyrate (PHB). Under nitrogen limitation, more carbon flux is directed to PHB synthesis while growth is inhibited with diminishing overall carbon utilization, similar to the suboptimal carbon utilization during glycolysis-derived pyruvate decarboxylation. This study reconfigured the central carbon network of Halomonas bluephagenesis to improve PHB yield theoretically and practically. It was found that the downregulation of glutamine synthetase (GS) activity led to a synchronous improvement on PHB accumulation and cell growth under nitrogen non-limitation condition, increasing the PHB yield from glucose (g/g) to 85% of theoretical yield, PHB titer from 7.6 g/L to 12.9 g/L, and from 51 g/L to 65 g/L when grown in shake flasks containing a rich N-source, and grown in a fed-batch cultivation conducted in a 7-L bioreactor also containing a rich N-source, respectively. Results offer better metabolic balance between glucose conversion efficiency and microbial growth for economic PHB production.

中文翻译：

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在高含氮培养基存在下合成多羟基丁酸酯 （PHB） 的工程盐单胞菌蓝噬机制


微生物生长和生物制品合成（包括细胞内聚酯聚羟基丁酸酯 （PHB））之间存在权衡。在氮限制下，更多的碳通量被引导到 PHB 合成，而生长受到抑制，整体碳利用率降低，类似于糖酵解衍生的丙酮酸脱羧过程中的次优碳利用。本研究从理论和实践上重构了 Halomonas bluephagenesis 的中心碳网络，以提高 PHB 产量。研究发现，在氮非限制性条件下，谷氨酰胺合成酶 （GS） 活性的下调导致 PHB 积累和细胞生长同步改善，将葡萄糖 （g/g） 的 PHB 产量提高到理论产量的 85%，PHB 滴度从 7.6 g/L 增加到 12.9 g/L，在含有丰富 N 源的摇瓶中生长时从 51 g/L 增加到 65 g/L， 并在同样含有丰富 N 源的 7-L 生物反应器中进行的补料分批培养中生长。结果为经济的 PHB 生产提供了葡萄糖转化效率和微生物生长之间更好的代谢平衡。