Influence of growth rate (µ) on the specific penicillin production rate (qPen) during a fermentation with the filamentous fungus Penicillium chrysogenum

Abstract

Nowadays, antibiotics are a crucial part of modern medicine. As generally known, the first one which was discovered by Alexander Fleming by accident, is penicillin. Penicillin is a bactericide substance which is produced by the filamentous fungus Penicillium chrysogenum, next to other fungi species, under carbon source limited conditions. Though nowadays fermentation conditions are highly optimized for maximal production rates, there is still room for further process optimization which is topic of several research groups worldwide targeting different aspects which may lead to the desired results. The scientific approaches are various. One of them is the the impact of the growth rate (). The growth rate is in the main focus of this Thesis. As described for different strains, the viable growth rate is linked to the specific penicillin production rate, qpen. The aim of my master thesis was to examine if the stated correlation does exist for the here applied penicillin V producing strain by comparing the qpen as well as the absolute penicillin concentrations of fed-batch cultivations with different constant, viable growth rates and to identify optimal conditions. Finally, the resulting relation was explored under oxygen limited conditions. In order to compare different set points, it was necessary to establish an adequate control strategy which enabled to reach and keep the aimed specific growth rate. Therefore, a soft sensor for the specific growth rate was used which was based on the measurement of the viable biomass via capacitance measurements. The method was optimized throughout the Thesis and controlled with adequate atline as well as offline methods. After establishing an adequate control strategy, several cultivations were performed with different set points and the outcomes evaluated. Therefore, different criteria for data evaluation were used and thus the dependency of the specific penicillin production rate on the specific growth rate determined. Finally, one cultivation with a certain set point was reproduced but with a decreased dissolved oxygen level of 4% in order to explore the correlation between viable growth rate the specific growth rate and viable specific penicillin production rate under oxygen limited conditions. The resulting relation between and qpen was similar as previously published by Douma et al., 2010, revealing a specific growth rate dependence of the specific penicillin production rate. The low oxygen level of 4% of the last cultivation negatively affected the specific penicillin production rate, leading to decreased specific penicillin production rates throughout the process. Nevertheless, several cultivations with different set points have to be performed in order to specify the results.