Nitric oxide dioxygenase: An enzymic function for flavohemoglobin

Nitric oxide (NO(•)) is a toxin, and various life forms appear to have evolved strategies for its detoxification. NO(•)-resistant mutants of Escherichia coli were isolated that rapidly consumed NO(•). An NO(•)-converting activity was reconstituted in extracts that required NADPH, FAD, and O(2), was cyanide-sensitive, and produced NO(3)(−). This nitric oxide dioxygenase (NOD) contained 19 of 20 N-terminal amino acids identical to those of the E. coli flavohemoglobin. Furthermore, NOD activity was produced by the flavohemoglobin gene and was inducible by NO(•). Flavohemoglobin/NOD-deficient mutants were also sensitive to growth inhibition by gaseous NO(•). The results identify a function for the evolutionarily conserved flavohemoglobins and, moreover, suggest that NO(•) detoxification may be a more ancient function for the widely distributed hemoglobins, and associated methemoglobin reductases, than dioxygen transport and storage.