bioreactor studies of heterologous protein production by ...

Nasi et ai.. 1988) and recombinant S. cerevisiae (Sode et aL, 1988; Wak and Gainer, 1989;
Yang and Shu, 1996). However. a gend exptanation for the above improved plasmid
staw is stin lacking. The proposed model may help us to undentand the stabiünng
mechanism. As derived in the model development section, the &t-onier decay constants
of the irnmobiüzed ce11 system cm be dexribed by Equation (6.24) as shown below:
while the fmt-order decay constants of the comsponding free ce11 system can be
expressed as Equation (5.29) as shown below:
y, = k, = pD
Compuuig Equations (5.29) with (6.24). ir is seen that the decay constants of the
immobilized ceU system are always less than those of the conesponding free cell sysrem as
long as the bionlm is existing in the bioreactor ( Xi > O ). Further analysis shows that the
reduced apparent decay constant is due to a reduced specific gowth nte in the
immobilized ceIl system. According to Equations (5.17) (p = D) and (6.17)
(Pi =x+xi DX ). the specific pwth rate of the immobihd cells is aiways lower than thrt
of the correspondhg frce ceUs at sme dilution rate. Equation (6.24) &O shows that the
apparent decay constants decrease with increasing biofilm concentration but inc~ase with
uicreasing dilution rate because of the changes in the specific growth rate. These
observations are confirmed by the experimental results kted in Table 6.1.