Sensitivity of recombinant fermentation with run-away plasmids: A structured analysis of the effect of dilution rate

A recently validated four-compartment model is used to describe intra-cellular dynamics during fermentations with recombinant microorganisms containing temperature-sensitive (run.-away) plasmids. The time-dependent sensitivities with respect to the dilution rate have been computed for normal and run-away replication. During normal replication the cells are most sensitive in the early stage of fermentation, and the intra-cellular compartment containing RNA and ribosomes is more sensitive than the other three lumped components. This is explained through a buffering effect. During run-away replication the sensitives are either constant or increase slowly with time, and there is a shift in the relative sensitivities of the intra-cellular components. All sensitivities except that of the substrate increase as the dilution rate increases.