Metabolic Reprogramming and Proteome Reallocation Accompany Loss of Respiratory Oscillations in Yeast Accelerostat

Respiratory oscillations are a hallmark of glucose-limited yeast chemostats, yet how growth rate shapes their emergence and collapse remains unclear. Here, we combined accelerostat cultivation with quantitative metabolomics and proteomics to characterize the transition from oscillatory to non-oscillatory metabolism in Saccharomyces cerevisiae under aerobic, glucose-limited conditions. Respiratory oscillations were maintained at low growth rates, attenuated at intermediate rates, and no longer observed at higher rates, coinciding with the onset of ethanol formation. Metabolomics analysis showed that oscillatory dynamics were most pronounced in tricarboxylic acid cycle intermediates and trehalose, whereas glycolysis and the pentose phosphate pathway exhibited weaker oscillations and instead adjusted pool sizes with growth rate. Quantitative proteomics further indicated that loss of oscillations was accompanied by non-uniform proteome reallocation, including increased representation of translation, glycolysis, energy metabolism, and amino acid biosynthesis, together with reduced relative allocation to buffering and proteostasis-related functions. Together, these results indicate a growth rate-associated physiological transition in glucose-limited yeast, in which the disappearance of oscillatory behavior during accelerostat cultivation is associated with a shift from respiratory to respiro-fermentative metabolism and coordinated reorganization of the proteome.