Abstract
Continuous-culture population dynamics of recombinant bacteria are predicted with a structured kinetic model. The instantaneous specific growth rates of the plasmid-bearing and plasmidfree cells are explicitly calculated from their metabolic activities. The resultant growth-rate differential (between plasmid-bearing and plasmid-free cells) is dynamic and changes over the course of a fermentation. Further, the growth-rate differential is a function of dilution rate. We present the experimental determination of model constants governing plasmid replication and foreign protein expression for a host/vector systemE. coli RR1 [pBR329]. For a different experimental system, we estimate the increased polypeptide expression from a DNA insert solely from the instability population dynamics. Stability predictions agree quite well with experimental observations from the literature and our lab.
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Bentley, W.E., Kompala, D.S. Stability in continuous cultures of recombinant bacteria: A metabolic approach. Biotechnol Lett 12, 329–334 (1990). https://doi.org/10.1007/BF01024426
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DOI: https://doi.org/10.1007/BF01024426