Oxygenases

Oxygenases are enzymes that catalyze the incorporation of molecular oxygen (O2) into a substrate or into the product formed during a reaction. They are essential in diverse biological processes, including the metabolism of xenobiotics, the synthesis of hormones and signaling molecules, and the degradation of complex natural products. By introducing oxygen into organic molecules, oxygenases can alter polarity, reactivity, and biological activity.

Oxygenases are commonly divided into two main classes: monooxygenases and dioxygenases. Monooxygenases transfer one atom of O2 into the substrate while reducing the other atom to water or hydrogen peroxide. They include cytochrome P450 enzymes, flavin-dependent monooxygenases, and non-heme iron(II)/2-oxoglutarate-dependent monooxygenases. Dioxygenases incorporate both atoms of O2 into the substrate, often causing ring opening or dihydroxylation; many are involved in aromatic compound degradation and lipid metabolism. Examples include intradiol and extradiol dioxygenases and lipoxygenases.

Mechanistically, oxygenases rely on various cofactors and electron donors. Cytochrome P450 enzymes use a heme iron and require electrons from NADPH (via a reductase system). Flavin-dependent monooxygenases use flavin cofactors (FAD or FMN). Non-heme iron(II) and 2-oxoglutarate-dependent enzymes use Fe(II) and the co-substrate 2-oxoglutarate to activate O2 for substrate oxidation.

Oxygenases have wide physiological and environmental roles, including drug metabolism, biosynthesis of natural products, and bioremediation. They are also exploited in biotechnology and synthesis for regio- and stereoselective hydroxylation and oxidation of complex substrates.