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A simple, structured model was developed to describe the growth and product formation behavior of two recombinant strains of Saccharomyces cerevisiae (JG176 and JG180), both overproducing extracellular proteinase A. The model parameters were estimated to data from continuous fermentations obtained at steady-state conditions. Model predictions show good agreement with experimental data obtained by batch fermentations. The two concerned organisms are distinguished from each other by the type of promoter on the plasmids controlling the proteinase A expression. The proteinase A transcription is controlled by the natural proteinase A promoter in JG176 and by a tpi promoter in JG180. By means of experiments and simulations, the extracellular product formation from the two strains with different promoter systems was compared in batch and continuous fermentations. The results showed that the proteinase A formation kinetic from JG176 was a combination of growth and nongrowth associated (production in the stationary growth phase), whereas the proteinase A formation from JG180 was truly growth associated (production in the exponential growth phase). In both batch and continuous cultivations JG176 gave the highest product concentrations and volumetric productivities.

Overexpression of the homologous protein proteinase A (PrA) in Saccharomyces cerevisiae has been achieved by inserting the PrA gene (PEP4) with its own promoter on a 2µ multicopy plasmid. With this system the specific PrA production rate was found to be described well by a linear function of the oxidative glucose metabolism, the reductive glucose metabolism, and the oxidative ethanol metabolism, with a significant lower yield resulting from the reductive glucose metabolism compared with the oxidative glucose metabolism. To describe the experimental data, a simple mathematical model has been set up. The model is based on an assumption of a limited respiratory capacity as suggested by Sonnleitner and Kä ppeli but extended to describe production of an extracellular protein. The model predicts correctly the critical dilution rate to be between 0.15 and 0.16 h −1 , the decrease in the biomass yield above the critical dilution rate, and the production of proteinase A at different dilution rates. Both the experimental data and model simulations suggest that the optimum operating conditions for protein production is just at the critical dilution rate.

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