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Gewählte Master / Diploma Thesis:

Markus Brillmann (2016): Controlled physiological dynamics for quantification of physiological capacities and influencing inclusion body properties & the specific product titer.
Master / Diploma Thesis - Institut für Biotechnologie, BOKU-Universität für Bodenkultur, pp 63. UB BOKU obvsg FullText

Data Source: ZID Abstracts
A bottleneck of downstream process efficiency in bioprocesses for production of pharmaceuticals was evoked by the established approach of separating up- and downstream development in pharmaceutical industry. This bottleneck could be targeted using an integrated approach to bioprocess development aiming for an overall efficiency increase of protein production processes in pharmaceutical industry. In this context, this work attempted to bridge the gap between USP and DSP development by trying to affect product attributes and the specific product titer by imposing controlled dynamic physiological changes in USP. For this purpose a recombinant protein production process using Escherichia coli (E. coli) as a host with a product in form of intracellular protein aggregates, so called inclusion bodies (IB) was used. The effect of the dynamics on the IB properties namely solubility and purity of the IBs as well as the specific product titer was investigated. Regarding the controlled physiological dynamics, controlled oscillations in the specific substrate uptake rate qs were carried out. The oscillations were described by their qs mean, qs amplitude and the frequency of the feed rate changes. These descriptors of the oscillations were used as factors in a 2 level full factorial design of experiment (DoE). The specific product titer, together with the solubility kinetics, the solubilisation yield and the IB purity were responses of this DoE. A correlation of the solubilisation kinetics and the amplitude of qs oscillations was shown within this thesis. This finding implies a possibility to affect the IB solubility kinetics already in USP. Furthermore the qs mean of the oscillations negatively affected the specific product titer. A decline in maximal physiological capacity without metabolite formation (qs crit) over time after induction was quantified. In respect of this a significant correlation between the decline in qs crit and the qs mean of the culture was shown.

1.Mitwirkender: Kasper Cornelia

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