Practice question

Aerobic metabolism inevitably generates reactive oxygen species including superoxide radical anion and hydrogen peroxide via single-electron leakage from respiratory flavoproteins and autoxidation of reduced ferredoxins that damage solvent-exposed iron-sulfur clusters, DNA bases and unsaturated lipids. Bacteria have evolved exquisite sensing transcription factors that regulate defensive regulons. OxyR in Escherichia coli contains highly reactive cysteines C199 and C208 that when oxidized by low micromolar H2O2 form a reversible intramolecular disulfide bond driving conformational change to active tetramer that binds promoters and activates transcription of katG catalase-hydroperoxidase, ahpCF alkyl hydroperoxide reductase, dps ferritin-like DNA-binding protein that sequesters iron, and gorA glutathione reductase. PerR in Gram-positive Bacillus subtilis senses peroxide through metal-catalyzed histidine oxidation at the regulatory site where bound Fe2+ or Mn2+ mediates Fenton-mediated oxidation, causing derepression of regulon including catalase KatA and peroxiredoxins AhpC. SoxR contains a solvent-exposed [2Fe-2S] cluster oxidized directly by superoxide and redox-cycling agents like paraquat, inducing transcription of soxS regulator which in turn activates sodA manganese superoxide dismutase, fumC fumarase C resistant to ROS, and acrAB tolC efflux pump. Together these three factors orchestrate metal sequestration, DNA protection and enzymatic detoxification.