Indole peroxygenase activity of indoleamine 2,3-dioxygenase

The heme enzyme indoleamine 2,3-dioxygenase (IDO) was found to catalyze the oxidation of indole by H2O2, with generation of 2- and 3-oxoindole as the major products. This reaction occurred in the absence of O-2 and reducing agents and was not inhibited by superoxide dismutase or hydroxyl radical scavengers, although it was strongly inhibited by L-Trp. The stoichiometry of the reaction indicated a one-to-one correspondence for the consumption of indole and H2O2. The O-18-labeling experiments indicated that the oxygen incorporated into the monooxygenated products was derived almost exclusively from H-2 O-18(2), suggesting that electron transfer was coupled to the transfer of oxygen from a ferryl intermediate of IDO. These results demonstrate that IDO oxidizes indole by means of a previously unrecognized peroxygenase activity. We conclude that IDO inserts oxygen into indole in a reaction that is mechanistically analogous to the "peroxide shunt" pathway of cytochrome P450.