Research of the working group „Microbial Fermentation“ is focussed on bioprocess development for the
economic production of recombinant proteins and DNA in E. coli. The overall approach of our work is
based on improved understanding of the complex phenotypic behaviour of a few selected host/vector
systems in order to gain optimal exploitation production organism. Therefore an integrated systems
approach is applied to overcome the unpredictability of impact and responses of recombinant protein
production on host cell metabolism. To enhance the monitoring capabilities a broad spectrum of on-line
and off-line experimental techniques using a variety of biochemical-physical principles has been
established. In addition to classical state variables on-line signals are gained from dielectric spectroscopy,
multi-wave fluorescence and in future also from proton transfer reaction mass spectrometry. The hidden
information of the thus acquired data is extracted by application of chemometric techniques to predict
complex variables like the content of biomass, product and plasmid copy number.

Transcriptome and proteome (DIGE) technology has been established to monitor the global impact of
recombinant protein expression on host metabolism. In addition, specific genome inserted
promoter-reporter constructs designed to monitor transcription level of key regulatory genes are applied.

Collaboration with experts in the field was established to analyse and interpret the generated data by
state of the art bioinformatics tools and yielded deeper insight into the cellular regulatory networks
related to recombinant protein production. Model based predictions will be further developed to unravel
the dynamics of host cell response aiming at improved process operation.