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S. cerevisiae is a widely used organism in biotechnological production and as a model organism for education. The yeast can growth anaerobically where sugar is reduced to ethanol but also aerobically with full reduction of sugar through the TCA cycle. In addition to that the yeast shows also the so  called “Crabtree” effect where under aerobic condition and high sugar availabilities ethanol is produced as byproduct [1]. In aerobic cultivations the Crabtree effect needs to be avoided to ensure full conversion of sugar into biomass and product without the formation of ethanol. One way to avoid this is a  strict limitation of sugar by employing a low nutrient feed rate or a low dilution rate in continuous cultivation. On the other hand, this strict limitation yields in low turnover rates.

Figure 1 Different metabolic pathways of S. cerevisiae and an exemplary dynamic experiment and model fit including all metabolic states Within this thesis best nutrient addition strategies are explored to find the best trade-off between high growth and turnover rates and low ethanol production through  he “Crabtree” effect. The Study uses wildtype S. cerevisiae in batch and fed-batch operation with different feed addition rates. The growth, respiratory quotient, substrate uptake and ethanol production rate are determined for the different feed phases. Based on the collected dataset a commonly used  inetic yeast model [1] is fitted to find out physiological properties of the strain and the model is used to propose optimal (interesting) feed regimes, which are potentially verified in Lab-scale. This model assisted process development strategy ensures to find out best dynamic feed supply with a lower  amount of expensive experimentation.

[1] Sonnleitner, B., & Käppeli, O. (1986). Growth of Saccharomyces cerevisiae is controlled by its limited respiratory capacity: formulation and verification of a hypothesis. Biotechnology and bioengineering, 28(6), 927-937.