Over the past four decades, many O2-activating enzymes have been found to contain oxygen-bridged diiron clusters.  Studies of these enzymes have yielded significant insight into the mechanisms that are used to activate oxygen, but soluble methane monooxygenase (MMO) has yielded perhaps the most complete view of the discrete steps in the catalytic process.  Additional steps and detailed characterization of the intermediates in this rich system continue to emerge and some of these will be described.  The MMO intermediates have been useful in the discovery and characterization of intermediates in several other newly recognized enzyme systems.  However, detailed studies of these enzymes have shown that oxygenase chemistry can be implemented and regulated in ways that differ from those described for MMO.  This will be illustrated using three examples: p-amino phenylalanine �-monooxygenase (CmlA), amino-chloramphenicol amine oxygenase (CmlI), and aldehyde deformylating oxygenase (ADO).  CmlA supports the diiron cluster in a different protein fold than MMO, but both require the binding of a protein partner to regulate catalysis.  However, the primary effect of binding is distinct: In MMO, partner binding controls substrate access to the diiron cluster, whereas in CmlA, complex formation appears to activate the cluster for reaction by inducing ligand exchange.  CmlI catalyzes a 6-electron oxidation of an arylamine to a nitroaryl group, apparently using a peroxo intermediate rather than the high valent dinuclear Fe(IV) intermediate Q of MMO.  Finally, ADO appears to use both a peroxo intermediate and a high valent Q-like intermediate to carry out different types of oxygenation reactions in the same active site. This large mechanistic diversity may arise from relatively small differences in the first and second sphere environments of the diiron clusters. Supported by NIH GM40466 and GM100943.

Diiron clusters in biology: Diverse chemistry from a common structure

248th National Meeting (2014)

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