bioreactor studies of heterologous protein production by ...

4. increased enzyme production was achieved in the airlift bioreactor compared to the
stirred-tank bioreactor. Higher glucoamylase productivity (70 %) was obtained in batch
cultures. in continuous suspension culture, it was also show that the enzyme production
decreased more rapidly in the stined-tank bioreactor because plasmid loss was faster than
in the airW bioreactor. This was possibly due to the vigorous fluid movement and wide
variation of shear forces caused by agitation. Airüft bioreacton provide more uniform
h ydmdynarnic and mas transfer c haracteristics. Double selection pressure was used to
select and maintah the recombinant strain. The selected strain showed better production
performance than the original suah in both airlift and stured-tank bioreactors.
5. Based on this work and the iitenture, a semi-senrctwed metabolic model was
developed for describing ceii growth. subsuate consumption. ethanol formation and
utilization, plasmid loss and recombinant protein production of recombinant yeast By
combining the Monod equation and segregational instabüity kinetics with the key
chmcteristics in yeast metabolism, the proposed model has feamres of simpiicity and
accuncy. The proposed model simulated the Crabtree effect. diamic growth, plasmid los
and recombinant protein production. The model contains 18 parameters which cm be
estimated fmm either experimentaI data or iiterature idormation. Most of the parameters
are generd and suitable for different yeast recombinant saains. When the model was
applied to the barch and continuous fermentations of the present recombinant yeast
(C468/pGAC9), excellent agreement between mode1 predictions and experimentai results
was achieved for giucose, ceil mas, ethanol, glucoamylase and fraction of plasmid-bearing