Yeast increases glycolytic flux to support higher growth rates accompanied by decreased metabolite regulation and lower protein phosphorylation

Supply of Gibbs free energy and precursors are vital for cellular function and cell metab-olism have evolved to be tightly regulated to balance their supply and consumption. Precursors and Gibbs free energy are generated in the central carbon metabolism (CCM), and fluxes through these pathways are precisely regulated. However, how fluxes through CCM pathways are affected by posttranslational modification and allosteric regulation remains poorly understood. Here, we integrated multi- omics data collected under nine different chemostat conditions to explore how fluxes in the CCM are regulated in the yeast Saccharomyces cerevisiae. We deduced a pathway-and metabolism-specific CCM flux regulation mechanism using hierarchical analysis combined with mathematical modeling. We found that increased glycolytic flux associated with an increased specific growth rate was accompanied by a decrease in flux regulation by metabolite concen-trations, including the concentration of allosteric effectors, and a decrease in the phos-phorylation level of glycolytic enzymes.

Automated summary

Supply and regulation of Gibbs free energy and precursors in cellular metabolism are essential for cellular function. In this study, we used multi-omics data under different conditions to investigate the regulation of central carbon metabolism (CCM) in yeast. We identified a metabolism-specific CCM flux regulation mechanism, which is affected by posttranslational modification and allosteric regulation.