Monooxgenases, mixed function oxidases (MFO)

The discovery of enzymes capable of catalyzing the activation of molecular oxygen - oxygenases - dates back to 1955 and the work of Osamu Hayaishi and Howard Mason (Hayaishi et al., 1955; Mason et al., 1955) who independently showed the incorporation of oxygen atoms from atmospheric oxygen rather than from water into organic substrates.

Hayaishi introduced the term monooxygenase to designate oxygenases that incorporate a single atom of oxygen into an organic substrate, while Mason introduced the term mixed function oxidase (mfo) to designate the different fates of the two atoms of oxygen: reduction to water and oxidation of an organic substrate. Both terms are therefore equivalent to designate P450 enzymes (even though some P450s can also catalyze reactions that do not involve oxygen at all).

In the late 20th century, many authors used mfo with a different meaning, apparently assuming that “mixed function” referred to the many known substrates of P450 enzymes, not the original intent of Mason. Currently, the term mfo is no longer used, but it is found in many old papers.

Mason stated that “the enzymes which catalyze reactions of molecular oxygen occur in three principle classes: (i) oxygen transferases [now known as dioxygenases], (ii) mixed function oxidases, and (iii) electron transferases. The first class catalyzes the transfer of a molecule of molecular oxygen to substrate. The second class catalyzes the transfer of one atom of the oxygen to substrate; the other atom undergoes two-equivalent reduction. The third class catalyses the reduction of molecular oxygen to hydrogen peroxide or to water.” (Mason, 1957).

Hayaishi (1974) summarized the historical background of the discovery of oxygenases. In that review he stated that “the term “hydroxylase” has been used by some investigators; however, this term is misleading and would be better avoided because not all hydroxylation reactions are catalyzed by monooxygenases”. This advice has largely been ignored, except in rare cases (Feyereisen and Durst, 1978).

P450s are not the only monooxygenases, see also flavin monooxygenases (FMOs).