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

Baez A, Shiloach J - Microb. Cell Fact. (2014)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20892, MD, USA. yossi@nih.gov.

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.

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Related in: MedlinePlus

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.
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Fig1: 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.

Mentions: When cells are exposed to high extracellular oxygen concentration, oxygen diffuses through the membranes and abstract electrons from reduced flavoenzymes to produce partially reduced oxygen species such as superoxide (O2-) and hydrogen peroxide (H2O2) [5,8,43,44]. Since ROS production-rate is proportional to collision frequency of oxygen and redox enzymes, the rate of O2- and H2O2 formation inside the cells depends directly on the oxygen concentration in the extracellular environment [4,5,44,45]. The association between hyperoxia and accumulation of ROS was shown in 1982 by Crapo and colleagues [46,47]. In later publications, it was shown that cultures of CD14+ monocyte and HeLa-20 cells exposed to 40% O2 and 80% O2 respectively produced 2-fold higher ROS amounts than cultures under normal atmospheric oxygen concentration [41,48]. Similarly, Entamoeba histolytica and Drosophila melanogaster flies exposed to high-oxygen environment (90-95% O2) showed 2-fold increases in ROS accumulation compared with flies exposed to normal oxygen conditions [49,50]. Using isolated mitochondria, it was shown that the majority of ROS detected in the cells were derived from the mitochondrial electron transport chain [41]. This was also established in bacteria, where the main source of endogenous superoxide (O2-) was found to be the respiratory chain [4,51]. It was also demonstrated that the formation rate of O2- increase in proportion to the oxygen concentration [4]. Hence, it was proposed that at hyperoxia conditions, the main ROS accumulated in the mitochondrial matrix is H2O2. The proposed steps for its accumulation are the following: when cells are exposed to an increasing oxygen concentration, there is higher leakage of electrons from complex I and III of the respiratory chain leading to an increase in superoxide production as described in FigureĀ 1. This superoxide is immediately converted to H2O2 by the mitochondrial superoxide dismutase [42]. At lower oxygen concentrations, catalases and glutathione peroxidase systems minimize the accumulation of H2O2 [44], but at higher oxygen concentrations, these antioxidant defenses are overwhelmed resulting in accumulation of H2O2 which can diffuse freely from the mitochondria reaching targets that can be damaged such as dehydratases and DNA [5,8].Figure 1


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

Baez A, Shiloach J - Microb. Cell Fact. (2014)

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.
© Copyright Policy - open-access
Related In: Results  -  Collection

License 1 - License 2
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getmorefigures.php?uid=PMC4279996&req=5

Fig1: 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.
Mentions: When cells are exposed to high extracellular oxygen concentration, oxygen diffuses through the membranes and abstract electrons from reduced flavoenzymes to produce partially reduced oxygen species such as superoxide (O2-) and hydrogen peroxide (H2O2) [5,8,43,44]. Since ROS production-rate is proportional to collision frequency of oxygen and redox enzymes, the rate of O2- and H2O2 formation inside the cells depends directly on the oxygen concentration in the extracellular environment [4,5,44,45]. The association between hyperoxia and accumulation of ROS was shown in 1982 by Crapo and colleagues [46,47]. In later publications, it was shown that cultures of CD14+ monocyte and HeLa-20 cells exposed to 40% O2 and 80% O2 respectively produced 2-fold higher ROS amounts than cultures under normal atmospheric oxygen concentration [41,48]. Similarly, Entamoeba histolytica and Drosophila melanogaster flies exposed to high-oxygen environment (90-95% O2) showed 2-fold increases in ROS accumulation compared with flies exposed to normal oxygen conditions [49,50]. Using isolated mitochondria, it was shown that the majority of ROS detected in the cells were derived from the mitochondrial electron transport chain [41]. This was also established in bacteria, where the main source of endogenous superoxide (O2-) was found to be the respiratory chain [4,51]. It was also demonstrated that the formation rate of O2- increase in proportion to the oxygen concentration [4]. Hence, it was proposed that at hyperoxia conditions, the main ROS accumulated in the mitochondrial matrix is H2O2. The proposed steps for its accumulation are the following: when cells are exposed to an increasing oxygen concentration, there is higher leakage of electrons from complex I and III of the respiratory chain leading to an increase in superoxide production as described in FigureĀ 1. This superoxide is immediately converted to H2O2 by the mitochondrial superoxide dismutase [42]. At lower oxygen concentrations, catalases and glutathione peroxidase systems minimize the accumulation of H2O2 [44], but at higher oxygen concentrations, these antioxidant defenses are overwhelmed resulting in accumulation of H2O2 which can diffuse freely from the mitochondria reaching targets that can be damaged such as dehydratases and DNA [5,8].Figure 1

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: Biotechnology Core Laboratory, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda 20892, MD, USA. yossi@nih.gov.

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.

Show MeSH
Related in: MedlinePlus