Superoxide dismutase (SOD) was first isolated by Mann and Keilis (1938) and its catalytic function, which consists to dismutate O2- into molecular oxygen and hydrogen peroxide, was discovered in 1969 by McCord and Fridovich [9]. Mammals have two forms of SOD isozymes: the manganese SOD (Mn-SOD), present in the mitochondria, and the copper/zinc SOD (Cu/Zn-SO), present in

the cytoplasm [10, 11]. In plants, SOD have been classified into three distinct types on the basis of their metal cofactor: Cu/Zn-SOD (in the cytosol and chloroplasts), Mn-SOD (in mitochondria), and Fe-SOD (often in chloroplasts) [12–14]. There are three known SOD in E. coli: MnSOD, FeSOD GSK2879552 and Compound Library mouse CuZnSOD. The two first are located in the cytoplasm and the last in the periplasmic space [15]. A distinct additional fourth class of SOD containing nickel selleck products (NiSOD) was recently discovered in Streptomyces

[16, 17] and cyanobacteria [18]. SOD-driven dismutation was the only biological mechanism identified for scavenging superoxide anion radicals until the early 1990′s. McCord et al. [19] established a correlation between oxygen tolerance and SOD production and suggested that SOD was the single most important enzyme for enabling organisms to survive in the presence of molecular oxygen. They proposed that the hypersensitivity of obligate anaerobes to oxygen was a consequence of SOD deficiency. However, most anaerobic organisms, which indeed lack SOD, show various degrees of tolerance to oxygen when they are occasionally exposed

to this molecule in their environments. Two novel iron-sulphur-containing proteins that detoxify superoxide molecules were then discovered in sulphate-reducing and hyperthermophilic anaerobes: desulfoferrodoxin (Dfx) in Desulfovibrio desulfuricans, Desulfovibrio vulgaris Hildenbourgh [20] and Desulfoarculus baarsii [21], neelaredoxin (Nlr) in Desulfovibrio gigas [22] and superoxide reductase (SOR) in Pyrococcus furiosus [23]. This revealed the existence of alternative mechanisms for ROS detoxification in anaerobes. The Oxalosuccinic acid function of these proteins was first studied in 1996 by Dfx complementation of superoxide detoxication activity in E. coli SOD mutants [24]. Later, Nlr from Treponema pallidum [25] and D. gigas [26] were also shown to complement such SOD mutants. Liochev and Fridovich [27] suggested that Dfx catalyzes the reduction of superoxide rather than its dismutation, and that it uses cellular reductants such as NAD(P)H. Subsequently, the Dfx enzyme was confirmed as an oxidoreductase [23–25, 27]. Finally, the superoxide reductase activity of those proteins were established by two groups [21, 23]. Dfx and Nlr proteins have different numbers of iron sites: both contain a similar C-terminal single iron-containing site (centre II) but also has Dfx a second N-terminal site (centre I) [22, 28].