A semiempirical model to control the production of a recombinant aldolase in high cell density cultures of Escherichia coli

A semi-empirical mathematical model for recombinant rhamnulose 1-phosphate aldolase (RhuA) production in high cell density cultures of Escherichia coli has been developed. An unstructured and non-segregated approach allowed to identify the inducer–biomass ratio (I/X) as the key parameter influencing initial specific production rate and specific growth rate reduction after induction. Biomass, substrate and RhuA concentration profiles have been properly fitted in fed-batch cultures induced by an IPTG pulse at different I/X ratio ranging from 0 to 3 μmol IPTG·g-1dry cell weight. The model has been validated firstly as able to predict recombinant aldolase and biomass production. In addition, since glucose accumulation in the induced period, which is an indicator of activity reduction by proteolysis, can be anticipated, the model has been used for control purposes with excellent results.

► An unstructured model is applied to predictive control of recombinant rhamnulose-1-phosphate aldolase production in E. coli fed-batch cultures.
► The model incorporates the effect of pulse induction on both growth rate and protein production at different induction loads.
► The model predicts glucose accumulation that is an indicator of activity reduction.