Methane Monooxygenase - Soluble Methane Monooxygenase (MMO) Systems - Proposed Catalytic Cycle and Mechanism

Proposed Catalytic Cycle and Mechanism

From the MMOH_red, the diiron centers react with the O₂ to form intermediate P. This intermediate is a peroxide species where the oxygens are bound symmetrically, suggested by spectroscopic studies. However, the structure is not known. Intermediate P then converts to intermediate Q, which was proposed to contain two antiferromagnetically coupled high-spin FeIV centers. This compound Q with its diamond core is critical to the oxidizing species for MMO.

There are two mechanisms suggested for the reaction between compound Q and the alkane: radical and nonradical. The radical mechanism starts with abstraction of the hydrogen atom from the substrate to form QH (the rate determining step), hydroxyl bridged compound Q and the free alkyl radical. The nonradical mechanism implies a concerted pathway, occurring via a four-center transition state and leading to a “hydrido-alkyl-Q” compound. As of 1999, the research suggests that the methane oxidation proceeds via a bound-radical mechanism.

It was suggested that the transition state for the radical mechanism involves a torsion motion of the hydroxyl OH ligand before the methyl radical can add to the bridging hydroxyl ligand to form the alcohol. As the radical approaches, the H atom of the alkane leave the coplanar tricoordinate O environment and bends upward to create a tetrahedral tetracoordinate O environment.

The final step for this reaction is the elimination of the alcohol and the regeneration of the catalysts. There are a few ways in which this can occur. It could be a stepwise mechanism that starts with the elimination of the alcohol and an intermediate Fe-O-Fe core, and the latter can eliminate the water and regenerate the enzyme through a 2e- reduction. On the other hand, it can start with a 2e- reduction process of bridging the O1 atom to give a water molecule, followed by elimination of the alcohol and regeneration of the enzyme. In addition, it is possible that there is a concerted mechanism whereby the elimination of the methanol occurs spontaneously with 2e- reduction of the bridging O1 center and regeneration of the catalyst.