Effect of elevated oxygen concentration on bacteria, yeasts, and cells propagated for production of biological compounds

Abstract

The response of bacteria, yeast, and mammalian and insects cells to oxidative stress is a topic that has been studied for many years. However, in most the reported studies, the oxidative stress was caused by challenging the organisms with H2O2 and redox-cycling drugs, but not by subjecting the cells to high concentrations of molecular oxygen. In this review we summarize available information about the effect of elevated oxygen concentrations on the physiology of microorganisms and cells at various culture conditions. In general, increased oxygen concentrations promote higher leakage of reactive oxygen species (superoxide and H2O2) from the respiratory chain affecting metalloenzymes and DNA that in turn cause impaired growth and elevated mutagenesis. To prevent the potential damage, the microorganisms and cells respond by activating antioxidant defenses and repair systems. This review described the factors that affect growth properties and metabolism at elevated oxygen concentrations that cells may be exposed to, in bioreactor sparged with oxygen enriched air which could affect the yield and quality of the recombinant proteins produced by high cell density schemes.

Figure 1

Elevated oxygen triggers intracellular ROS accumulation. The ubisemiquinone intermediates present in complexes I and III of the respiratory chain are the primary source of univalent reduction of oxygen into superoxide (O₂ ^.-) (indicated by stars). At over-oxygenation conditions, electrons leak from complexes I and III generating superoxide increases. Superoxide is converted immediately to hydrogen peroxide (H₂O₂) by manganese superoxide dismutase (MnSOD) or copper/zinc superoxide dismutase (Cu/ZnSOD). At normoxic conditions, the catalases and peroxidase systems minimize the accumulation of H₂O₂ but at higher oxygen concentrations; these antioxidant defenses can be overwhelmed and the accumulating H₂O₂ diffuse freely from the mitochondria (dashed lines) reaching targets that can be damaged such as dehydratases and DNA. Abbreviations: CoQ, coenzyme Q10; Cyt C, cytochrome C; GPX, glutathione peroxidase; IM, inner membrane; IMS, intermembrane space; OM, outer membrane.