The Yeast Cyclin-Dependent Kinase Routes Carbon Fluxes to Fuel Cell Cycle Progression

Cell division entails a sequence of processes whose specific demands for biosynthetic precursors and energy place dynamic requirements on metabolism. However, little is known about how metabolic fluxes are coordinated with the cell division cycle. Here, we examine budding yeast to show that more than half of all measured metabolites change significantly through the cell division cycle. Cell cycle-dependent changes in central carbon metabolism are controlled by the cyclin-dependent kinase (Cdk1), a major cell cycle regulator, and the metabolic regulator protein kinase A. At the G1/S transition, Cdk1 phosphorylates and activates the enzyme Nth1, which funnels the storage carbohydrate trehalose into central carbon metabolism. Trehalose utilization fuels anabolic processes required to reliably complete cell division. Thus, the cell cycle entrains carbon metabolism to fuel biosynthesis. Because the oscillation of Cdk activity is a conserved feature of the eukaryotic cell cycle, we anticipate its frequent use in dynamically regulating metabolism for efficient proliferation. [Display omitted] •Cell cycle progression triggers global changes in metabolism•The cell cycle kinase Cdk1 activates the trehalase Nth1 at the G1/S transition•Active Nth1 releases trehalose to fuel biosynthesis during S/G2/M•Trehalose utilization enables cell cycle progression even during acute starvation Ewald et al. discovered that cell cycle progression triggers global changes in the yeast metabolome and identified one underlying mechanism. At the G1/S transition, Cdk1 phosphorylates and activates the trehalase Nth1 to funnel trehalose into glycolysis. Trehalose utilization supports cell cycle progression in poor nutrient environments.