Model-Based Evolutionary Operation Design for Batch and Fed- Batch Antibiotic Production Bioprocesses

The control policy determination for batch and fed-batch antibiotic production bioprocesses is an important practical issue due to the high added value of these bioproducts. Since it is highly desirable to optimize the antibiotic production, several methods have been proposed aimed at this objective. Once having a mathematical model for the bioprocess, the optimization problem can be formulated within the framework of Pontryagin's maximum principle and of the optimal control theory to determinate the best control trajectory for certain key manipulated variables, such as temperature, pH, and substrate feed rate. In this chapter, applications of these model-based techniques to optimize and control antibiotics production bioprocesses are reviewed and new aspects are emphasized. The cases analyzed included the optimization of the substrate feed rate in a fed-batch reactor and of the temperature in a batch reactor during penicillin fermentations. The main contributions of this study were: (i) the proposition of a different procedure for calculating the second switching time of substrate feed rate, (ii) the application of simpler numerical methods to solve the two-point boundary-value problem associated with the temperature profile optimization, and (iii) the demonstration that the non-isothermal operation is more productive in antibiotic than the operation under constant temperature.