NITRIC-OXIDE DIOXYGENASE - AN ENZYMATIC FUNCTION FOR FLAVOHEMOGLOBIN

oxide (NO.) is a toxin, and various life forms appear to have evolved strategies for its detoxification. NO.-resistant mutants of Escherichi a coli were isolated that rapidly consumed NO., An NO.-converting acti vity was reconstituted in extracts that required NADPH, FAD, and O-2, was cyanide-sensitive, and produced NO3-. This nitric oxide dioxygenas e (NOD) contained 19 of 20 N-terminal amino acids identical to those o f 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 gase ous NO.. The results identify a function for the evolutionarily conser ved flavohemoglobins and, moreover, suggest that NO. detoxification ma y be a more ancient function for the widely distributed hemoglobins, a nd associated methemoglobin reductases, than dioxygen transport and st orage.