bioreactor studies of heterologous protein production by ...

productivity irrespective of the mode of operation of the reactor (Walls and Gainer, 1991).
Several immobüization related eff~nbanced plasmid stability, hcreased ceIl
concentmtion, and operation at high dilution ratc-contributed to enhanced productivity.
In view of the many experimental obswratiow. irnmobüization can be concluded
to have a near universal stabilizing effect on recombinant cek It is thought that
immobilization cm reduce the probability of plasmid-loss by reducing or eliminating
phsrnid structural and segregational instabifitiies Several hypotheses have been to
proposed to explain this effect, but the speeific mechanisms remah unclear.
23.2. Possible Stabiiizing Mechanism
Stabilization that accompanies kmobilization rnay have several possible som, including
one or more of the following:
1 ) hrnobilization may maintain or increase plasmid copy number (Sayadi et aL, 1987).
2) Compartmeniaüzation in the immobüiring gel may separate the plasmid-bearing ce&
from plamid-fiee celis, thereby eliminating their growth cornpetition (De Taxis Du
Poet et al,, 1986).
3) Diffusionai nutrient Limitations in the gel rnay cause a growth rate gradient in the
ma&, and hence morphologicd and physiologicai changes in imrnobihd ceUs (De
Taxis Du Poet ct al., 1987).
4) The dose proximity of immobilized œlls couid promote d e r of plasmid DNA
between two populations by either conjugation or traosformation (Huang et aL, 1993).