bioreactor studies of heterologous protein production by ...

(1987) model aliows for plasmid instability due to growth of piasmid-firee ceils in spite of
selection pressure. and that due to plasmid Ioss. Moreover, the model dinctly relates to
rneaîurable macroscopic parameters. The results predicted by thû model agree with
experimental data Furthemore. the model shows that in chemostat mDred culture
without selection pressure, coexistence is impossible if p- > p* and p > O. If this occurs,
the original plasmid-bearing population will be evenmaüy replaced by plasmid-fiee cm.
However. the models about recombinant yeast disnissed above dedt only with the
kinetics of plasmici instability. These models did not assimilate the information regarding
the metaboiic pahways in yeast S. cerevisiae. They were unable to simulate the dynamics
of ceil growth, substrate consurnption and gene product formation. in ment years, oniy a
few saidies regarding modelling of recombinant yeast addnssed ali of these aspects.
By utüizing the avaiiable knowledge on the behaviwr of recombinant S.
cerevisiae. a model for ceii growth, heterogeneous protein production and plasmid
segregation was fomuiated to examine specific experimental data by Coppella and
Dhujati (1990). Three catabolic pathways of yeast: glucose fermentation. glucose
oxidation and ethanol oxidation were considered in their modeL Three simplined enzyme
pools were assumed to be responsible for regulating the above catabolic pathways. These
enzyme pools could be either induced or depressed by glucose concentration depending
their hinctionality. The thne catabolic pathways couid be simoltaneously activated. By
combining catabolic pathways, stoichiometry. mas balance. piasmid segregation and