| Summary: | The epidermal growth factor (EGF) is a molecule of potent mitogenic activity that accelerates the healing of wounds and ulcers of different tissues in the human body. Over the last years, some institutions of the Havana Western Scientific Pole in Cuba have been developing novel therapeutic products and projects using the human EGF (hEGF) like Heberprot-P® (CIGB) and Cimavax EGF® (CIM). Currently, the growing demand for this molecule has led to strategies being focused on a significant increase in the production capacity of the hEGF. The aim of this work was to increase productivity in the hEGF fermentation process by a combined study of physiological variables, cultivation media and bioreactor operation mode. The influence of culture medium components and the operation during fermentation on the homogeneous production of hEGF and the producer strain growth characteristics were evaluated. A 3.5-fold increase in EGF productivity was obtained by using high cell density fed-batch fermentation process. This fermentation process allowed reaching a cell concentration of 241.6 ± 18.8 g/L (wet mass) and hEGF production of 259.2 ± 37.2 mg/L. This is the first report of hEGF fermentation process expressed in yeasts with productivity of 4.82 ± 0.57 mg/L·h. As part of the analysis, we also discuss the impact of maintaining the highest hEGF expression on productivity in the fermentation process.
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