Spectral analysis of a nonideal bioreactor for a recombinant fermentation with run-away plasmids

Abstract

An earlier application of spectral analysis to an isothermal, perfectly mixed, fed-batch fermentation [11] showed that it provides insight into the performance and reveals significant differences between key extra-cellular and intra-cellular (recombinant) variables. To enable application on a practically useful scale, the methodology has been extended to a bioreactor with temperature variation, incomplete mixing of the broth and Gaussian disturbances. For the same system, β-galactosidase produced by a recombinant E. coli strain, there are again differences between the rDNA and its protein, on the one hand, and the concentration and mass fraction of recombinant cells, on the other. For certain combinations of the dilution rate and the degrees of mixing, the bioreactor is only marginally stable, implying that a sufficiently large disturbance can trigger unstable behavior.