Process models for production of beta-lactam antibiotics.

Great progress has been made in the modelling of biotechnical processes using filamentous microorganisms. This paper deals with cultivations of Penicillium chrysogenum for the production of Penicillin and of Acremonium chrysogenum for the production of Cephalosporin C. The properties of the processes and the existing models are reviewed. Models are presented for both processes that consider aspects which are important for industrial cultivation. The process model for Penicillin production is based on a detailed morphological description of growth of hyphal filaments and pellets. The model allows for simulation of the production process including the preculture and considering the inhomogenous pellet population. It opens new possibilities for understanding the complex kinetics of the process and improvement of its control. The structured segregated model for Cephalosporin C production considers soy oil as second carbon source besides sugar. The application of the model for dynamic optimization of feeding strategies by Iterative Dynamic Programming is demonstrated. As an alternative approach, modelling of the Cephalosporin production by an artificial neural network is discussed.