Does the non-heme monooxygenase sMMO share a unified oxidation mechanism with the heme monooxygenase cytochrome P-450?

Until recently, the majority of experts would have replied "yes" to the question in the title of this commentary. In fact, the answer is not so evident. Re cent investigations have permitted us to gain insight into the similarities and the differences between the mechanisms of these two remarkable monooxygenases. In the generally accepted mechanism of cytochrome P-450, reductive activation of dioxygen and the presence of an external electrophile leads to heterolytic O-O bond cleavage to yield water and a highly electron-deficient terminally bound iron oxenoid species that is capable of attacking unactivated hydrocarbons by an electrophilic mechanism. The recently suggested "bridge mechanism" for sMMO involves homolytic O-O bond cleavage of a diferric "side-on" peroxide intermediate to yield a bridged intermediate bis-mu-oxo-diiron(IV) species, in which both oxygen atoms are derived from the dioxygen molecule. In contrast to terminal oxenoid species, this bridged diiron(IV) intermediate has stronger steric selectivity for substrates; this explains the unusual selectivity observed in sMMO alkane oxidation.