Coordination Dynamics of Iron is a Key Player in the Catalysis of Non‐heme Enzymes

Abstract Mononuclear nonheme iron enzymes catalyze a large variety of oxidative transformations responsible for various biosynthesis and metabolism processes. Unlike their P450 counterparts, non‐heme enzymes generally possess flexible and variable coordination architecture, which can endow rich reactivity for non‐heme enzymes. This Concept highlights that the coordination dynamics of iron can be a key player in controlling the activity and selectivity of non‐heme enzymes. In ergothioneine synthase EgtB, the coordination switch of the sulfoxide radical species enables the efficient and selective C−S coupling reaction. In iron(II)‐ and 2‐oxoglutarate‐dependent (Fe/2OG) oxygenases, the conformational flip of ferryl‐oxo intermediate can be extensively involved in selective oxidation reactions. Especially, the five‐coordinate ferryl‐oxo species may allow the substrate coordination via O or N atom, which may facilitate the C−O or C−N coupling reactions via stabilizing the transition states and inhibiting the unwanted hydroxylation reactions.