Structured models for recombinant human interleukin-11 fermentation

In this work, batch and fed-batch cultivations of a recombinant Escherichia coli (E. coli), which expressed Interleukin-11 (IL-11) as a fusion protein, were performed in a 12 L bioreactor. Time profiles of total RNA, total protein, rhIL-11 protein, and cell and glucose concentrations were obtained and the results were simulated with a three-compartment model designed previously, a new empirical model, and a new four-compartment model. Numerical simultaneous integration of the model equations was done using a fourth order Runga-Kutta method. Although the three-compartment model was able to fit most of the batch fermentation results reasonable well, it failed to depict cell growth delay caused by induction when induction effects were serious. With only 7 model parameters, the newly developed empirical model was able to fit both pre-induction processes and post-induction ones with reasonable accuracy. It was therefore used to model both batch and fed-batch fermentation results where growth inhibition caused by induction was pronounced. The four-compartment model was constructed to characterize induction effects in a profound way. Based on the simulation results, this model exhibited similar performance to that of the empirical model in fitting the fermentation data. In addition it was successfully used for providing guidance to the determination of optimal induction time.