Non-Heme Mono-Iron Enzymes: Co-Substrate-Dependent Dioxygen Activation

Non-heme mono-iron (NHMI) dioxygen (O2) activating enzymes are widely distributed in nature. They are involved in many fundamental biological pathways, and catalyze a stunningly broad array of oxidative reactions, including some of the most challenging chemical transformations, such as hydroxylation and halogenation on unactivated carbon-hydrogen bonds and carbon-carbon (C(sp2)-C(sp3)) bond formation. This chemical versatility is achieved by the exquisite control of O2 activation by the mono-iron centers with simple yet well evolved structures. The studies on NHMI enzymes have exploded in recent years with discoveries of new enzymes and new reactions. The mechanistic understanding of NHMI enzymes has also been dramatically improved. In this article, we provide a comprehensive summary of NHMI enzyme studies, focusing on those published in the recent 15 years with the emphases on the iron center coordination environments of various enzymes and the reaction mechanisms they support.