Evaluation of heat induction strategy for recombinant human growth hormone expression in fed-batch fermentation

The high cell density cultivation (HCDC) of a recombinant E. coli producing human growth hormone (hGH) under different heat induction strategies has been reported. In this paper the effect of heat shock temperature, its duration and post-induction temperature, at two levels on cell growth and death, hGH production and its degradation, substrate utilization and by-product formation were investigated by full factorial experimental design. The results showed that heat shock temperature was the most effective factor on hGH production having approximately 75.8% of total contribution. There was no significant accumulation of substrate or by-product in culture medium during HCDC in all experiments. Thirty two percent of cells were subjected to lysis during the heat induction at 42C for 20 min followed by 37C for 4h. Biologically active recombinant hGH was produced comprising 13% of total cell protein without degradation. An empirical equation was employed to describe the relationship between three factors and hGH production during HCDC.