Monooxygenase

Monooxygenase is an enzyme that catalyzes the incorporation of one atom of molecular oxygen into an organic substrate with reduction of the other oxygen atom to water. They are distinct from dioxygenases, which insert both atoms of O2 into substrates.

Two major classes are flavin-containing monooxygenases (FMOs) and cytochrome P450 monooxygenases. FMOs use flavin cofactors (FAD or FMN) and NADPH to activate O2 and hydroxylate soft nucleophiles such as sulfurs, nitrogens, and some carbon atoms. Cytochrome P450 monooxygenases contain a heme iron in the active site and are driven by electrons supplied by NADPH through redox partners (often a P450 reductase). They catalyze hydroxylation, epoxidation, and dealkylation across a broad range of substrates, including drugs and natural products. Other monooxygenases, including copper- and non-heme iron-dependent enzymes, occur in bacteria, fungi, and plants, but are less well characterized in humans.

Mechanistically, oxygen activation typically proceeds via formation of an activated oxygen species that inserts one atom into the substrate and reduces the second to water, with the exact intermediates depending on the enzyme class. Cofactors, cellular location (cytosolic or membrane-bound), and substrate scope determine specificity.

Biological roles include metabolism and detoxification of xenobiotics, biosynthesis of natural products, and degradation of environmental pollutants. In biotechnology, monooxygenases are exploited for selective hydroxylation and oxidation steps in pharmaceutical synthesis and bioremediation, with ongoing research to engineer selectivity and stability.