bioreactor studies of heterologous protein production by ...

estimated by using Equation (6.24) and the values of p obtained in the correspondhg Gee
celi system. Table 6.1 shows that a reasonable agnement between the predicted and
measund fint-order decay constants was achieved It is ako noted hm Table 6. L that
the predicted decay constant is les than the cornpondhg measured one. This is because
the iUXId immobilized celi system may deviate fimm the assurned idealized bionlm mode!.
nius. in the present case the reduced specific growth rate alone is adequate to explain the
enhanced apparent stability in the immobilized ceU system.
Equation (6.24) also shows that the apparent decay constants are directly
proponiond to the probabiüty of plasmid loss. In genenl. enhmced plasmid stability by
Unrnobilization may be also due to a reduced pmbability of plasmid loss. The pmbability
of plasmid loss in irnmobilized celi system may be reduced due to increased plasrnid copy
number. close contact, the effects of compartmentiilization and mas uansfer. It was
found that the copy number of the plasmid increased with decreasing specinc growth rate
(Sayadi et al. 1987; Bentiey and Kompah, 1989). Since the immobilized ceüs gow slower, an
increased plasmid copy number could be another reason for the inneased pbmid stability in
imrnobiikd ce11 systems. There is also some evidence that budding of imrnobilized ceik may
be delayed whk decoupled DNA repiication and polysaccharide synthesis continue (Ghose,
1988). Additional DNA replication wilî change the gene bel of the o&Fp~g of the
Unmobilized celis. in the case of the immobilized recombinant cells, the delay of the budding
combined with con~uing pWd DNA nplication would result in increased plasmid copy
number and ensure that the offkpring ceiis would be more likely to bear plasmids. Fuiany, the