Stability of continuous culture with recombinant organisms

It was found that both poor selection pressure and a variable rate of plasmid loss were present in the system studied and that both have significant effects on continuous reactor operation. At least some of these effects were analyzed by a simple model. At this point, experimental analysis for extracellular levels of tryptophan sufficient to support X- growth (1-4 mg/l) has given contradictory results. This has at least partially indicated the effect may be an intracellular one, and thus the culture history would be critical in such experiments. Since the system studied is not atypical of recombinant cultures, it leads one to speculate on the generality of the phenomena and its extent in other cultures. If important, the use of double auxotrophs or auxotrophs that are mutant in a metabolite for which the cell has a greater growth requirement should be used. Additionally, the presence of higher copy numbers in yeast at lower growth rates also leads one to speculate on how these apparently contradictory phenomena are related.