Mathematical modeling as a tool to describe and optimize heterologous protein production by yeast cells in aerated fed-batch reactor

In this work, two recombinant yeast strains, the prototrophic non-conventional Zygosaccharomyces bailii [pZ3KlIL-1beta] and the auxotrophic Saccharomyces cerevisiae BY4741[PIR4-IL1beta], both producing human interleukin-1beta, have been cultured in aerated fed-batch using glucose as limiting substrate. A mathematical model of the fed-batch reactor has been developed, based on mass balance equations of the main process variables: biomass, glucose and product, and implemented with kinetic expressions to explain the yeast behaviour within the aerated fed-batch reactor. In the case of Z. bailii, the mathematical model evidenced the suitability of the fermentative inoculum with respect to the respiratory one at the start of the exponential feeding. In the case of the auxotrophic S. cerevisiae BY4741, the modellistic approach has permitted to highlight a strong deviation from the expected behaviour and quantify the glucose amount that is spent for maintenance rather than for growth, thus impairing the outcome of the bioprocess