Cybernetic modeling based on pathway analysis for Penicillium chrysogenum fed-batch fermentation.

A macrokinetic model employing cybernetic methodology is proposed to describe mycelium growth and penicillin production. Based on the primordial and complete metabolic network of Penicillium chrysogenum found in the literature, the modeling procedure is guided by metabolic flux analysis and cybernetic modeling framework. The abstracted cybernetic model describes the transients of the consumption rates of the substrates, the assimilation rates of intermediates, the biomass growth rate, as well as the penicillin formation rate. Combined with the bioreactor model, these reaction rates are linked with the most important state variables, i.e., mycelium, substrate and product concentrations. Simplex method is used to estimate the sensitive parameters of the model. Finally, validation of the model is carried out with 20 batches of industrial-scale penicillin cultivation.