Max Planck Institute for Terrestrial Microbiology and Center for Synthetic Microbiology (SYNMIKRO), D-35043, Marburg, Germany.
State Key Laboratory of Microbial Technology, Shandong University, Qingdao, 266237, China.
Nat Commun. 2023 Apr 15;14(1):2173. doi: 10.1038/s41467-023-37957-0.
The operation of the central metabolism is typically assumed to be deterministic, but dynamics and high connectivity of the metabolic network make it potentially prone to generating fluctuations. However, time-resolved measurements of metabolite levels in individual cells that are required to characterize such fluctuations remained a challenge, particularly in small bacterial cells. Here we use single-cell metabolite measurements based on Förster resonance energy transfer, combined with computer simulations, to explore the real-time dynamics of the metabolic network of Escherichia coli. We observe that steplike exposure of starved E. coli to glycolytic carbon sources elicits large periodic fluctuations in the intracellular concentration of pyruvate in individual cells. These fluctuations are consistent with predicted oscillatory dynamics of E. coli metabolic network, and they are primarily controlled by biochemical reactions around the pyruvate node. Our results further indicate that fluctuations in glycolysis propagate to other cellular processes, possibly leading to temporal heterogeneity of cellular states within a population.
中心代谢的运作通常被认为是确定性的，但代谢网络的动态性和高度连通性使其有可能容易产生波动。然而，要描述这种波动，需要对单个细胞中的代谢物水平进行时间分辨的测量，这在小型细菌细胞中仍然是一个挑战。在这里，我们使用基于Förster 共振能量转移的单细胞代谢物测量，结合计算机模拟，来探索大肠杆菌代谢网络的实时动态。我们观察到，饥饿的大肠杆菌受到糖酵解碳源的逐步暴露，会在单个细胞中引起丙酮酸的细胞内浓度的周期性大幅波动。这些波动与大肠杆菌代谢网络的预测振荡动力学一致，并且主要受丙酮酸节点周围的生化反应控制。我们的结果进一步表明，糖酵解的波动会传播到其他细胞过程中，可能导致群体内细胞状态的时间异质性。
