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bioRxiv · 10.1101/2023.07.06.547923

Cross-regulation between proteome reallocation and metabolic flux redistribution governs bacterial growth transition kinetics

Yuan, H.·Li, X.·Bai, Y.·Fu, X.
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Abstract

Bacteria need to adjust their metabolism and protein synthesis simultaneously to adapt to changing nutrient conditions. Its 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.

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Yuan, H., Li, X., Bai, Y., Fu, X.. 2023-07-07. Cross-regulation between proteome reallocation and metabolic flux redistribution governs bacterial growth transition kinetics. https://doi.org/10.1101/2023.07.06.547923

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