bioreactor studies of heterologous protein production by ...

The effixts of dilution rate on the activities of the pacemaker enzyme pools for
glucose fementation and gùicose oxidation pathways (Ci and C') are ppresented in Figure
5.7. CI iricreases with increasing dilution rate &ce the glacose flux increases with
inmashg dilution rate and CI is induced by the glucose flux. In contras& C2 demases
with increasing dilotion rate because of the repression by high glucose fim. Both CI and
Cr tend to be constant at high dilution rate, corresponding to full induction of CI and fidi
repression of C2. The specific growth rate for glucose fermentation (pi) is directly
proportional to the dilution rate due to inmasing CI and glucose concentration (G). The
specif~c growth rate for glucose oxidation (pz) i3 hcreases with increasing dilution rate,
then tends to be nearly constant at higher dilution rate, Uidicating that a saturated
respiratory capacity is reached (Sonnieitner and Kappeii, 1986). The ratio of pl to ~2
increase steadily with increasing dilution rate, suggesting that glucose oxidation is
dominant at low dilution rate and glucose fermentation predorninates at high dilution rate.
5.4.4. Plasmid Loss and Enzyme Production Decay Kinetics
As denved in Section 5-41, the plasmid los kinetics can be described by Equation (5.24b)
as shown below:
X+ = x,+ erp(-pDt) = X,' orp(-k,t) (5ab)
where k, = pD . a fim-order decay rate constant for plasmid los. Equation (5.24b)
shows that the decay of plasmid-bearing cells foiiows fim-order kinetics and the
concentration of plasmid-b&g c& decnases with culture the during continuous
culture,