Bacteria need to adjust their metabolism and protein synthesis simultaneously to adapt to changing nutrient conditions. It’s still a grand challenge to predict how cells coordinate such adaptation due to the cross-regulation between the metabolic fluxes and the protein synthesis. Here we developed a dynamic Constrained Allocation Flux Balance Analysis method (dCAFBA), which integrates flux-controlled proteome allocation and protein limited flux balance analysis. This framework can predict the redistribution dynamics of metabolic fluxes without requiring detailed enzyme parameters. We reveal that during nutrient up-shifts, the calculated metabolic fluxes change in agreement with experimental measurements of enzyme protein dynamics. During nutrient down-shifts, we uncover a switch of metabolic bottleneck from carbon uptake proteins to metabolic enzymes, which disrupts the coordination between metabolic flux and their enzyme abundance. Our method provides a quantitative framework to investigate cellular metabolism under varying environments and reveals insights into bacterial adaptation strategies.

中文翻译：

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蛋白质组重新分配和代谢通量重新分配之间的交叉调节控制细菌生长转变动力学

细菌需要同时调整其新陈代谢和蛋白质合成，以适应不断变化的营养条件。由于代谢流和蛋白质合成之间的交叉调节，预测细胞如何协调这种适应仍然是一个巨大的挑战。在这里，我们开发了一种动态约束分配通量平衡分析方法（dCAFBA），该方法集成了通量控制的蛋白质组分配和蛋白质限制通量平衡分析。该框架可以预测代谢通量的重新分布动态，而不需要详细的酶参数。我们发现，在营养物质上升期间，计算出的代谢通量的变化与酶蛋白动力学的实验测量一致。在营养物质下降期间，我们发现代谢瓶颈从碳吸收蛋白到代谢酶的转换，这破坏了代谢通量与其酶丰度之间的协调。我们的方法提供了一个定量框架来研究不同环境下的细胞代谢，并揭示了细菌适应策略的见解。