The regulation of metabolic pathways by polyphosphate accumulation and its application to fermentation technology

无机聚磷酸盐（polyP）是一种由数百个磷酸盐通过高能磷酸酐键连接而成的线性聚合物。由于polyP是由ATP通过polyP激酶（polyP kinase， PPK）合成的，因此polyP合成的调控被认为与细胞代谢和能量状态密切相关。之前我们发现，大肠杆菌中phoU突变刺激息肉p积累，导致参与几种代谢途径的基因表达发生变化。在这项研究中，我们分析了polyP积累与硝酸盐呼吸（NR）之间的关系，NR是大肠杆菌中phoU破坏引起基因表达改变的途径之一。通过对△PhoU菌株的分析发现，除了Phoregulon外，PhoU还存在一种新的调控NR通路的抑制功能。利用PPK进行下拉分析，揭示了PPK与参与TCA循环和NADH产生的蛋白的相互作用。这些结果提示多肽的合成与中枢代谢途径的调控有直接关系。

Inorganic polyphosphate (polyP) is a linear polymer of hundreds of phosphates linked by high-energy phosphoanhydride bonds. Since polyP is synthesized from ATP by polyP kinase (PPK), the regulation of polyP synthesis is thought to be closely related to the cellular metabolism and the energy status. Previously, we found that polyP accumulation stimulated by phoU mutation in Escherichia coli results in the changes in the expression of the genes involved in the several metabolic pathways. In this study, we analyzed the relationship between polyP accumulation and nitrate respiration (NR), one of the pathways found in the altered gene expression caused by phoU disruption in E. coli. The presence of a novel repression function of PhoU that regulates NR pathway besides Phoregulon was suggested from the analysis using a △phoU strain. The interaction of PPK to the proteins involved in TCA cycle and NADH production was revealed by pull-down analysis using PPK. These results suggest the direct relationship between polyP synthesis and the regulation of central metabolic pathway.