Cross regulation and central metabolism in bacteria

9405929 Wanner该建议是继续研究大肠杆菌中心代谢途径中的“交叉调节”。 交叉调节是指一个双组分调节系统中的一个反应调节子被另一个不同的调节系统所控制。 两个这样的控制作用于磷酸盐（PHO）调节子。 一个涉及CreC传感器激酶（其与其伴侣反应调节剂CreB一起由分解代谢物调节creABCD操纵子编码）;另一个涉及乙酰磷酸。 这两种控制似乎都很重要，因为每种控制都提供了一种将PHO调节子的控制（通过细胞外Pi的水平）与中心代谢途径偶联的方法，用于将细胞内Pi掺入ATP（代谢中的主要磷酰基供体）。 该提案的具体目标是：（i）鉴定由CreB-CreC双组分调节系统调节的基因;（ii）检查正常和突变细胞中的乙酰磷酸合成;和（iii）进行基因调节研究以评估交叉调节在细胞生理学中的重要性。 %细胞经历许多调整的中央代谢途径，以响应碳和能源。 这些调节需要不同细胞功能之间的高度调节相互作用，以允许细胞生长。 交叉调节为这些不同途径之间的协调调节提供了手段。 这项研究将集中在控制与磷代谢密切相关的基因的交叉调节（一种必需的营养素，其同化与中央代谢途径密切相关）。 虽然这些研究将完全在模型细菌大肠杆菌中进行，但结果可能适用于所有类型的细胞。 这是因为中央路径之间的统一性。 将探讨两种交叉调节机制。 一个涉及蛋白质磷酸化，这是控制调节蛋白（在所有细胞中）的重要过程。 另一个涉及一种小分子（乙酰磷酸），它似乎在控制（某些）已知受蛋白磷酸化影响的调节蛋白中起效应分子的作用。 ***

9405929 Wanner This proposal is to continue studies on "cross regulation" in central metabolic pathways of Escherichia coli. Cross regulation refers to the control of a response regulator of one two-component regulatory system by a different regulatory system. Two such controls act on the phosphate (PHO) regulon. One involves the CreC sensor kinase (which is encoded together with its partner response regulator CreB by catabolite regulatory creABCD operon); the other involves acetyl phosphate. Both of these controls appear to be important, for each provides a way to couple control of the PHO regulon (by the level of extracellular Pi) to pathways of central metabolism for the incorporation of intracellular Pi into ATP (the primary phosphoryl donor in metabolism). Specific aims of this proposal are: (i) to identify genes regulated by the CreB-CreC two- component regulatory system; (ii) to examine acetyl phosphate synthesis in normal and mutant cells; and (iii) to conduct gene regulation studies to assess the importance of cross regulation in cell physiology. %%% Cells undergo numerous adjustments of central pathways of metabolism in response to the carbon and energy sources. These adjustments require a high degree of regulatory interactions between and among different cellular functions in order to permit the cell to grow. Cross regulation provides a means for the coordinate regulation among these different pathways. This study will focus on cross regulation in the control of genes closely related to phosphorus metabolism (an essential nutrient whose assimilation is closely connected to central metabolic pathways.) Although these studies will be carried out entirely in the model bacterium Escherichia coli, the results are likely to pertain to all types of cells. This is because of the unity among central pathways. Two mechanisms of cross regulation will be explored. One involves protein phosphorylation, an important process for the control of regulatory proteins (in all cells). The other involves a small molecule (acetyl phosphate) which appears to act as an effector molecule in the control of (certain) regulatory proteins known to be affected by protein phosphorylation. ***