Rieske mono- and di- oxygenases (ROs) use a nonheme mononuclear Fe and a 12 Å-distant 2Fe2S Rieske cluster to catalyze an enormous range of oxidative reactions, which exceeds even those of cyt P450 and methane monooxygenase. Like the latter two oxygenases, the transfer of two electrons from NADH to the RO metal centers is required for reaction. Oxygen activation and insertion into substrates occurs at the mononuclear Fe(II) center, but one electron transfer from the reduced Rieske cluster is required at some point during the reaction cycle to observe product formation. The involvement of 2 electrons and oxygen at the mononuclear Fe suggests that at least three different types of reactive oxygen intermediates can be envisioned: (1) stepwise electron transfer with intermediate formation of a reactive Fe(III)-superoxo species, (2) two electron transfer to oxygen to form an Fe(III)-peroxo species, or (3) O-O bond cleavage of the peroxo-intermediate to form a high-valent reactive species. Ongoing biochemical and chemical biomimetic studies suggest that all three reactive oxygen species may be represented within the RO family despite nearly identical metal environments. Indeed, when presented with different substrates, a single RO enzyme may adopt two or more of these strategies depending on the relative ease of substrate oxidation versus the rate of electron transfer between metal centers










John Lipscomb (University of Minnesota)