Effect of an exponential feeding regime on the production ofRhodotorula araucariaeepoxide hydrolase inYarrowia lipolytica

Abstract

To evaluate the effect of and exponential feeding regime on the production of epoxide hydrolase (EH) enzyme in recombinant Yarrowia lipolytica in comparison to a constant feed strategy. An exponential feed model was developed and fermentations were fed at six different exponential rates. A twofold increase in EH productivity and a 15% increase in volumetric EH activity was obtained by applying exponential glucose feed rates in fed-batch cultivation. These responses were modelled to obtain a theoretical optimum feed rate that was validated in duplicate fermentations. The model optimum of 0.06 h(-1) resulted in a volumetric EH activity of c. 5500 U l(-1) h(-1) and a maximum activity of 206,000 U l(-1). This correlated well with model predictions, with a variance of <10%. The use of an exponential feed strategy at a rate of 0.06 h(-1) yielded best results for all key responses which show a clear improvement over a constant feed strategy. The study was the first evaluation of an exponential feed strategy on recombinant Y. lipolytica for the production of EH enzyme. The results suggest a strategy for the commercial production of a valuable pharmaceutical enzyme.