Penicillin fermentation: mechanisms and models for industrial-scale bioreactors

Even after many years of research and industrial practice, the production of penicillin G in fed-batch fermentation by Penicillium crysogenum continues to attract research interest. There are many reasons: the commercial and therapeutic importance of penicillin and its derivatives, the complexity of cell growth, and the impact of engineering variables, the last of which are significant in large bioreactors but are not yet fully understood. Extensive research has generated new information on the mechanisms of cellular reactions and morphological features of the mycelia and their role in the synthesis of the product. Given a choice of mechanisms, models of different degrees of complexity, for both cellular differentiation and bioreactor performance, have been proposed. The more complex models require and provide more information. They are also more difficult to evaluate and apply in automatic control systems for production-scale bioreactors. The present review considers the evolution of recent knowledge and models from this perspective.