ROLES OF MANGANESE AND IRON IN THE REGULATION OF THE BIOSYNTHESIS OF MANGANESE-SUPEROXIDE DISMUTASE IN ESCHERICHIA-COLI

Aerobic life-style offers both benefits and risks to living cells. The major risk comes from the formation of reactive oxygen intermediates (i.e. superoxide radical, O-2(-); hydrogen peroxide, H2O2; and hydroxy l radical, OH.) during normal oxygen metabolism, However, living cells are able to cope with oxygen toxicity by virtue of a unique set of an tioxidant enzymes that scavenge 0(2)(-) and H2O2, and prevent the form ation OH.. Superoxide dismutases (SODs; EC 1.15.1.1) are metalloenzyme s essential for aerobic survival. Escherichia coli contains two forms of this enzyme: an iron-containing enzyme (FeSOD) and a manganese-cont aining enzyme (MnSOD). In E. coli, MnSOD biosynthesis is under rigorou s control. The enzyme is induced in response to a variety of environme ntal stress conditions including exposure to oxygen, redox cycling com pounds such as paraquat which exacerbate the level of intracellular su peroxide radicals, iron chelation (i.e. iron deprivation), and oxidant s. A model for the regulation of the MnSOD has been proposed in which the MnSOD gene (sodA) is negatively regulated at the level of transcri ption by an iron-containing redox-sensitive repressor protein. The eff ect of ironchelation most probably results in removal of the iron nece ssary for repressor activity. Recent studies have shown that sodA expr ession is regulated by three iron-dependent regulatory proteins, Fur ( ferric uptake regulation), Fnr (fumarate nitrate regulation) and SoxR (superoxide regulon), and by the ArcA/ArcB (aerobic respiration contro l) system. The potential Fur-, Fnr- and ArcA-binding sites in the sodA promoter region have been identified by using different cis-acting re gulatory mutations that caused anaerobic derepression of the gene. An updated model is presented to accommodate these findings and explain t he biological significance of regulation by multi-regulatory elements in response to multi-environmental effectors.