Effects of oxygen on recombinant protein expression.

ABSTRACT

Efforts to increase cell growth and protein yields need to be complemented by the maintenance of the quality of the protein produced. Elevated oxygen pressure or rapid increases in oxygen content can cause oxidative stress within the cells, leading to oxidation of specific proteins and nucleotide sequences. In addition, transient or steady-state anoxic conditions can cause limitations in amino acid production and plasmid stability. Major pathways and mechanisms of oxidative damage to proteins expressed in bacteria are reviewed. Damage to nucleic acids involved in gene expression also is considered. The methodologies for identifying oxidative damage to macromolecules are improving but are not yet adequate for on-line feedback. This limits our ability to integrate information about these phenomena and the cellular responses into a quantitative model. Enough information is available, however, to consider changes in the time profile of dissolved oxygen as a cause for poor process performance.