Combined Metabolomic and Proteomic Profiling Reveals Hypoxia as A Cause of Lower Productivity on Scale-Up to A 5000-Liter CHO Bioprocess

摘要

In this study, we, for the first time, applied a combined proteomics and metabolomics approach for a systems biology study of an industrial scale CHO bioprocess. As shown in Figure 6, our results revealed that the cells underwent intermittent hypoxia in the 5-KL scale process, inducing excess ROS. Additional copper reduced the stress, and hence improved the viability at the 5-KL scale, albeit at a still lower level than the bench-top scale. The 20-L scale showed much less hypoxia and less excess ROS generation, resulting in little to no impact to productivity with the increased copper in the media. Oxygen mixing was clearly better for the small scale reactor, as expected.