bioreactor studies of heterologous protein production by ...

on metabolic pathways. In the fermentation industry, dissolved oxygen concentration is a
key parameter used to control mimbial growth and fermentation. Effects of dissolwd
oxygen on microbial metabolism have been extensive1y cW~Ï'bed (Ejiofor et al., 1996;
Car and Dawes, 1978; Chisti, 1989); however, the= is 1ittle information on how oxygen
affects the expression and Stability of plasrai& Tolentino and San (1988) showed that
piasrnid stability in recombinant E. coli was unaffected by DOT kvek It was observed
that the plasrnid was stable during a step change in the environment in which oxygen and
nitrogen were supplied altemately. In contrast, the concentration of dissolved oxygen
affected plasmid stability in a recombinant yeast (Lee and Hassan, 1987). Using a
glucose-limited chemostat culture. Lee and Hassan (1987) examined the effects of oxygen
tension and dilution rate on the stability and expression of külu toxin plasmid @AD&
10A) in wine yeast (MONtrachet 522). The recombinant yeast was grown in nitrogen-,
air-, and pure oxygen-sparged environments. The highest plasmid stabiiity was observed
in the air-sparged culture, suggesting the possibility of an optimum dissolved oxygen
concentration for greatest Stability of the plasmid. Simüar results were reported by Caunt
et ai. (1989) in studies of oxygen limitation on piasmid stabiiity in recombinant yeast
grown in a nonselective medium. The yeast strain was YN124ipLG669-z, which
produced P-galactosidase. Once the dissolved oxygen level was lowued to below 10% of
air saturation. the fraction of plamid-containing cells declined sharply (Cam et al.,
1989).