Effects of Oxygen Supply Modes on the Production of Human Growth Hormone in Different Scale Bioreactors

Recombinant Escherichia coli has been studied as a main host for recombinant protein productions, but it is still difficult to cultivate E. coli in a large industrial‐scale process due to the oxygen supply limitation. In this study, E. coli BL(21) harboring a new constructed plasmid (pEHUb‐hGH) was used for producing recombinant human growth hormone (r‐hGH) in 5‐L and 30‐L scale fermentors by supplying air and high purity oxygen, respectively, where the high purity oxygen was produced from a vacuum pressure swing adsorption (PSA). The impact of oxygen supply modes, i.e., air and high purity oxygen, on cell growth and r‐hGH production was investigated in different scale fermentors. In the case of high purity oxygen supply, the final cell density and r‐hGH concentrations were 63.0 and 4.8 g/L in the 5‐L fermentor, 51.6 and 4.0 g/L in the 30‐L fermentor, respectively. In addition, the productivity of r‐hGH was doubled in the 5‐L fermentor, and increased 4‐fold in the 30‐L fermentor, compared to the results obtained in the case of the air supply. The supply of high purity oxygen eliminated the oxygen limitation and acetate formation effectively, and apparently, did not affect the degradation of r‐hGH. This shows that the recombinant E. coli cultivation with high purity oxygen produced from PSA may provide an effective method for large‐scale industrial production of recombinant proteins. In the fed‐batch culture of E. coli BL(21) for producing recombinant human growth hormone (r‐hGH), the cell growth and r‐hGH production are seen to be significantly improved by supplying high purity oxygen. This demonstrates that supplying high purity oxygen may be effective for carrying out large‐scale, high cell density aerobic cultures.