Impact of process parameters on morphology, physiology and process performance of the filamentous fungus Penicillium chrysogenum

Abstract

Filamentous fungi are important industrial production organisms with a broad product portfolio ranging from bulk chemicals to therapeutic proteins. As morphology, physiology and productivity of these organisms are highly interlinked and influenced by process parameters, it is crucial to understand these interdependences for design and improvement of bioprocesses. Although it is long known that hydrodynamics and energy characteristics are influencing fungal morphology, numerous aspects are still unknown. Penicillium chrysogenum is used for antibiotic production since more than 70 years. Despite increasing bacterial immunity penicillins still constitute a major portion of anti-infectives. Yet, there is still room for process and strain optimization. While strain screening is in general carried out in shake flasks, bioreactors are used for production scale. As these two systems differ drastically, increased understanding of the effecting process parameters is crucial for scalability of processes. In this work the influence of process parameter with special emphasis on shaking and stirring on morphology, physiology and productivity is examined. A series of experiments is carried out in shake flasks and in bioreactor to investigate the impact of cultivation systems. As energetic characteristics were not measurable, correlations reported in literature are used as alternative method for their estimation. Cultivations are accompanied by a variety of analytical methods including an automatic, high-throughput method for thorough characterization of fungal morphology. The combination of established and novel analytical methods enables the examination of a broad range of aspects including morphology, viability, productivity and metabolic activity. Hence, deeper insight in the mechanisms controlling fungal characteristics and their interdependencies is gained.