Hydrocarbon Activation by Oxygenase Enzymes

Evidence for a radical intermediate includes C-H bond selectivities typical for a radical reaction and intramolecular isotope studies using substrates with CHD 

Methane is produced in enormous quantities in nature by methanogenic bacteria, but much of it is immediately consumed in aqueous environments by methanotrophic bacteria, which oxidize CH4 as their sole source of carbon and energy. Thus for the bonds in H2 and N2, the strong C-H bond in methane is activated biologically, in this case converted to methanol by the enzyme MMO76  

Two reducing equivalents from NAD(P)H are used to split the 0-0 bond of 02 as the first step. One oxygen atom is then reduced to water while the second is inserted into CH4 to give methanol. Although P-450 catalyzes similar reactions, only MMO can activate methane. It also can oxidize a large variety of other hydrocarbons up to C8, including halogenated and heterocyclic species. 

The crystal structure of the enzyme contains another workhorse dinuclear iron center, although here it is bridged by oxygen donor ligands such as glutamate in 18. 

The reduced form of MMO is oxidized by direct reaction with 02 and several intermediates are observed. The active species in the methane conversion is denoted as compound Q and is proposed to contain Fe centers bridged by glutamate and oxo groups, the first of its type in biology. 

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