There and back again: a metabolic journey through novel yeast physiology

Baker’s yeast (Saccharomyces cerevisiae) has long been a cornerstone of both research and industry, but the vast diversity of other yeast species and their potential applications is now coming into focus. This thesis explores how metabolic models, combined with physiological laboratory data, can address challenges in food industry and fundamental biology. In Chapter 2, we review the use of metabolic models in food industry and explore their potential in biotransformations, food safety, and flavor enhancement. A practical example of a metabolic model to address a problem in food industry is presented in Chapter 3. Rising sugar levels in grapes due to global warming lead to higher ethanol content in wine. The yeast Lachancea thermotolerans offers a solution by converting sugars into lactate, reducing ethanol levels while enhancing flavor. Using exometabolite fluxes, RNA-transcriptomics, and metabolic modeling, we uncovered that lactate production in this yeast is linked to nitrogen limitation during fermentation. In Chapter 4, we turn to Overflow metabolism, where in some yeast low-yield fermentation (Crabtree positive) is preferred to high-yield respiration under excess glucose and oxygen conditions. In this study we compared Crabtree-negative Pichia kluyveri to Crabtreepositive Saccharomyces cerevisiae. By integrating proteomics and quantitative physiology into proteome-constrained models, we found that the switch from respiration to fermentation is governed by proteome efficiency, a combination of catalytic efficiency and the composition of the electron transport chain. This study advances understanding of how proteome constraints influence yeast metabolism and offers insights into the evolutionary adaptations of these species. Finally, Chapter 5 discusses the challenges of applying data from well-studied species like S. cerevisiae to model the metabolism of novel yeasts, and introduces methods to calculate the proteome efficiency of metabolic pathways.