The rate of glucose metabolism sets the cell morphology across yeast strains and species.

Yeasts are a diverse group of unicellular fungi that have developed a wide array of phenotypes and traits over 400 million years of evolution. However, we still lack an understanding of the biological principles governing the range of cell morphologies, metabolic modes, and reproductive strategies yeasts display. In this study, we explored the relationship between cell morphology and metabolism in sixteen yeast strains across eleven species. We performed a quantitative analysis of the physiology and morphology of these strains and discovered a strong correlation between the glucose uptake rate (GUR) and the surface-area-to-volume ratio. ¹⁴C-glucose uptake experiments demonstrated that the GUR for a given strain is governed either by glucose transport capacity or glycolytic rate, indicating that it is rather the rate of glucose metabolism in general that correlates with cell morphology. Furthermore, perturbations in glucose metabolism influenced cell sizes, whereas manipulating cell size did not affect GUR, suggesting that glucose metabolism determines cell size rather than the reverse. Across the strains tested, we also found that the rate of glucose metabolism influenced ethanol production rate, biomass yield, and carbon dioxide transfer rate. Overall, our findings demonstrate that the rate of glucose metabolism is a key factor shaping yeast cell morphology and physiology, offering new insights into the fundamental principles of yeast biology.