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

Abstract:
Escherichia coli producing a plasmid DNA (pDNA) vaccine was cultivated in fedbatch mode at small scale (1 L) 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 0.42 mol L1 h1. The OTRMAX in the pressurized reactor with an overpressure of 8 bar was 0.5 mol L1 h1. In the small- and pilotscale 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.

Keywords:
DNA vaccines, E. coli, fermentation, high cell density, oxygen transfer

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