Simulation of a bioreactor to produce recombinant insulin

Abstract

This project has focused on the study, modelling and simulation of the fermentation process to produce recombinant proinsulin in Escherichia coli, as a key step in the process of manufacturing human insulin from the proinsulin method. Given the current market situation for this important protein, the project is based on the need to explore accessible, efficient and replicable production strategies on an industrial scale. To this end, a mathematical model based on differential matter balances was developed, which describes the evolution of the main variables of the process (biomass, glucose, volume and proinsulin) in a fed-batch culture. From this model, two operational configurations were implemented: one based on a single tank where both the growth and induction phases take place, and another in which these phases are carried out separately in a cyclic system of two connected tanks. Both strategies were simulated using Euler's method, applying a pH-stat type feed and with realistic operating conditions. The results obtained allowed the analysis of the dynamics of the system in each configuration, evaluating the evolution of the key variables and the productivity of the process. Finally, both configurations were compared under a scenario of continuous operation for 365 days, which allowed estimating the annual production of proinsulin in each case. Based on these results, the advantages and limitations of each strategy were analyzed, in order to reflect on which of the models is more viable depending on the specific operating conditions. This comparison seeks to serve as a guide for future implementations of the process on a larger scale, providing solid information for decision-making in industrial contexts