A novel systems dynamics model for simulation of yeast batch, fed-batch and continuous cultures.

Modelling of microbial cell cultures is essential for design, optimization and control of processes of biotechnological interest. Models can vary from the simple “black box” descriptions to more complex “cybernetic” approaches, but they usually lack flexibility in representing the microbial population dynamics including feedbacks from environment. On the contrary, the innovative model recently proposed [1] and based on the principle of Systems Dynamics, highlights how the decline and arrest of cell proliferation depends on the accumulation of self-produced inhibitory compounds in the medium. The model (developed in SIMILE and MATLAB R2012b) focused on the yeast Saccharomyces cerevisiae, a microorganism of major biotechnological importance, and considers the main metabolic routes of glucose assimilation during aerobic growth in batch, continuous and fed-batch reactors. Main feature of the model is represented by the metabolic shift between respiration and fermentation occurring in S. cerevisiae (a Crabtree positive yeast) at high sugar concentration, as a function of the levels of glycolysis process. The same modelling approach has been extended to Crabtree negative yeasts (Kluyveromyces sp.), to shed light on the Crabtree (glucose) effect, a “metabolic paradox” which still remains to be fully explained [2]. References [1] S. Mazzoleni, C. Landi, F. Cartenì, E. de Alteriis, F. Giannino, L. Paciello, P. Parascandola A novel process-based model of microbial growth: self-inhibition in Saccharomyces cerevisiae aerobic fed-batch cultures Microb Cell Fact, 14 (2015), p. 109 [2] T. Pfeiffer, A. Morley An evolutionary perspective on the Crabtree effect. Front Mol Biosci, 1 (2014), pp. 1–6