Calorimetric control for high cell density cultivation of a recombinant Escherichia coli strain

In order to achieve maximum productivity of recombinant proteins in Escherichia coli high cell density cultivation (HCDC) strategies have been the subject of many studies. The aim of this work was the application of calorimetric methods to HCDC. The specific growth rate of a recombinant E. coli strain producing green fluorescent protein (GFP) was controlled during fed-batch cultivations by estimating the specific growth rate from the measured heat flow produced by the cells. For the cultivation a standard 30 l laboratory bioreactor was used, which was extended in such a way that heat balancing is possible. The feed rate was adjusted by an adaptive controller such that the specific growth rate was kept on the desired set point value. On the basis of experimental investigations with a recombinant E. coli strain using glucose as limiting C-source it was demonstrated that the specific growth rate can be kept on a given set point value and biomass concentrations of up to 120 g l(-1) can be obtained, reproducibly.