bioreactor studies of heterologous protein production by ...

for plasmid maintenance function in growth media of any composition, such systems are
ideal for large-sale indusaial culture.
22.15. Genetic properties of host fells
interactions between the host ceIl and the plasmids artarmy play an important role m
maintenance of the phsrnid; hence, the properties of the host must also be considend m
any discussion of plasrnid stability. A certain plasmid transformed into dinuent mutants
of a host may display different stability characteristics in different mutants (Yu and Tang,
1991; Kikuchi and Toh-e, 1986). The host mutants may e t
plasmid partitioning,
replication. or amplincation, di of which relate to stability. Some evidence suggests that
the plasmids rnay utihe some fom of anchorage to a host cellular structure. hence leading
CO possible asymmetric inhentance upon cell division (Wu et al., 1987). For the seletion
system discussed in the above section. in order for the selection to be effective. it is
required that host mutants possess very Iow reversion frequencies. However, it is not easy
to obtain a very stable host mutant and much Mer work is needed in this regard.
The growth cycle of a host greatïy a&cts the processes of replication and
transcription of the plasmid, and that nlationship is bound to affect pIasmid stability.
Unfortunately, there is little data on the effects of physio10gW properties on plasmid
stability, and some results are inconsistent Mead et aL (1986) obsemd that the rate of
plasmid Ioss was reduced by aiîowing haploid populations to enter stationary phase
penodically. In conmt, for the 2 p based yeast hybrid pIasmids, Kleinrnan et al. (1987)