New Frontiers in Nonheme Enzymatic Oxyferryl Species

Abstract

AbstractNon‐heme mononuclear iron dependent (NHM−Fe) enzymes exhibit exceedingly diverse catalytic reactivities. Despite their catalytic versatilities, the mononuclear iron centers in these enzymes show a relatively simple architecture, in which an iron atom is ligated with 2–4 amino acid residues, including histidine, aspartic or glutamic acid. In the past two decades, a common high‐valent reactive iron intermediate, the S=2 oxyferryl (Fe(IV)‐oxo or Fe(IV)=O) species, has been repeatedly discovered in NHM−Fe enzymes containing a 2‐His‐Fe or 2‐His‐1‐carboxylate‐Fe center. However, for 3‐His/4‐His‐Fe enzymes, no common reactive intermediate has been identified. Recently, we have spectroscopically characterized the first S=1 Fe(IV) intermediate in a 3‐His‐Fe containing enzyme, OvoA, which catalyzes a novel oxidative carbon‐sulfur bond formation. In this review, we summarize the broad reactivities demonstrated by S=2 Fe(IV)‐oxo intermediates, the discovery of the first S=1 Fe(IV) intermediate in OvoA and the mechanistic implication of such a discovery, and the intrinsic reactivity differences of the S=2 and the S=1 Fe(IV)‐oxo species. Finally, we postulate the possible reasons to utilize an S=1 Fe(IV) species in OvoA and their implications to other 3‐His/4‐His‐Fe enzymes.