Comparison of oxygen enriched air vs. pressure cultivations to increase oxygen transfer and to scale-up plasmid DNA production fermentations

摘要

Escherichia coli producing a plasmid DNA (pDNA) vaccine was cultivated in fed-batch mode at small scale (1L) using oxygen-enriched air, and at pilot scale (50 L) using a pressurized bioreactor, to maintain aerobic conditions. In the small scale, the attained oxygen transfer rate (OTRmax) using an oxygen concentration in the inlet gas of 68.2%, reached 0.42mol L~(-1)h~(-1). The OTRmax in the pressurized reactor with an overpressure of 8 bar was 0.5 mol L~(-1)h~(-1). In the small- and pilot-scale cultivations, the final biomass concentrations (74 and 79 g/L, respectively), pDNA concentrations (236 and 215 mg/L), overall productivity and pDNA topology were very similar. Therefore, the pressurized cultivation is a viable option to scale up pDNA production processes.