bioreactor studies of heterologous protein production by ...

Impoolsup et ai. (1989a) and Hardjito et al (1993) reported that segregational instabiIity
(plasmid losslper generation) increased with increasing dilution rates in a culture of a
recombinant yeast in non-selective medium. The effect of dilution rate seerns to relate to
the medium used. When recombinant S. cerevisiae yeasts were continuously grown in
selective medium, plasmid instability was reported to decrease with increasing dilution
rates (Parker and DiBiasio, 1987; Lee and Hassan, 1988; Caunt et d., 1989; Da Silva and
Baiiey, 1991).
43.33. Estimation of Instability Parameters
The foliowing discussion refm to growth conditions when the specific growth rate of the
plasmid-bearing celis is not significantly different from plasmid-fnt ceB. It can be shown
that if the fraction of piasmid-bearing ceUs ( F ) follows a exponential decay pattern, then
plotting dB/dt venus B wi. give a straight line with a slope of = kI and an intercept of b
= kfi if F declines according to an exponential pattern (Eq.(4.3)). then we have:
Differentiating Eq. ( 15) and rearranging the mult yields:
Substini~g Eq. (4.15) into Eq. (4.16) gives: