Constant Growth Rate Can Be Supported by Decreasing Energy Flux and Increasing Aerobic Glycolysis

Fermenting glucose in the presence of enough oxygen to support respiration, known as aerobic glycolysis, is believed to maximize growth rate. We observed increasing aerobic glycolysis during exponential growth, suggesting additional physiological roles for aerobic glycolysis. We investigated such roles in yeast batch cultures by quantifying O2 consumption, CO2 production, amino acids, mRNAs, proteins, posttranslational modifications, and stress sensitivity in the course of nine doublings at constant rate. During this course, the cells support a constant biomass-production rate with decreasing rates of respiration and ATP production but also decrease their stress resistance. As the respiration rate decreases, so do the levels of enzymes catalyzing rate-determining reactions of the tricarboxylic-acid cycle (providing NADH for respiration) and of mitochondrial folate-mediated NADPH production (required for oxidative defense). The findings demonstrate that exponential growth can represent not a single metabolic/physiological state but a continuum of changing states and that aerobic glycolysis can reduce the energy demands associated with respiratory metabolism and stress survival. [Display omitted] •Increasing stress sensitivity and aerobic glycolysis during exponential growth•Global remodeling of metabolism during nine doublings at a constant rate•Parallel declines in respiration and in mitochondrial NADPH-producing enzymes•Time-series coverage of the yeast proteome Slavov, van Oudenaarden, and colleagues find that exponential growth at a constant growth rate can represent not a single metabolic/physiological state but a continuum of changing states characterized by different oxidative- and heat-stress resistance, protein expression, and metabolic fluxes. Metabolic fluxes that change during exponential growth include respiration, fermentation, NADH, and NADPH production.