Improving the batch-to-batch reproducibility in microbial cultures during recombinant protein production by guiding the process along a predefined total biomass profile.
In industry Escherichia coli is the preferred host system for the heterologous biosynthesis of therapeutic proteins that do not need posttranslational modifications. In this report, the development of a robust high-cell-density fed-batch procedure for the efficient production of a therapeutic hormone is described. The strategy is to guide the process along a predefined profile of the total biomass that was derived from a given specific growth rate profile. This profile might have been built upon experience or derived from numerical process optimization. A surprisingly simple adaptive procedure correcting for deviations from the desired path was developed. In this way the batch-to-batch reproducibility can be drastically improved as compared to the process control strategies typically applied in industry. This applies not only to the biomass but, as the results clearly show, to the product titer also.
Jenzsch
Marco
M
Zentrum für Bioverfahrenstechnik, Martin-Luther-Universitaet, Weinbergweg 22, c/o Biozentrum, 06120 Halle, Saale, Germany marco.jenzsch@biochemtech.uni-halle.de.
Gnoth
Stefan
S
Kleinschmidt
Martin
M
Simutis
Rimvydas
R
Lübbert
Andreas
A
D019149:Bioreactors / Q000382:microbiology*; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods; D049109:Cell Proliferation; D003198:Computer Simulation; D004867:Equipment Design; D019544:Equipment Failure Analysis; D004926:Escherichia coli / Q000502:physiology*; D005246:Feedback / Q000502:physiology; D008954:Models, Biological; D011786:Quality Control; D011994:Recombinant Proteins / Q000096:biosynthesis* / Q000302:isolation & purification*; D015203:Reproducibility of Results
D011994:Recombinant Proteins