Biosynthetic enzymes oxygenation reactions

Phenolic compounds are commonplace natural products Figure 24 2 presents a sampling of some naturally occurring phenols Phenolic natural products can arise by a number of different biosynthetic pathways In animals aromatic rings are hydroxylated by way of arene oxide intermediates formed by the enzyme catalyzed reaction between an aromatic ring and molecular oxygen... 

Analogous side-chain oxidations occur in various biosynthetic pathways. The neurotransmitter norepinephrine, for instance, is biosynthesized from dopamine by a benzylic hydroxylation reaction. The process is catalyzed by the copper-containing enzyme dopamine /3-monooxygenase and occurs by a radical mechanism. A copper-oxygen species in the enzyme first abstracts the pro-R benzylic hydrogen to give a radical, and a hydroxyl is then transferred from copper to carbon. 

Elucidating all the fascinating details of this reaction will require further mechanistic, structural, and model studies. Finally, the discovery of self-processing redox enzymes (see Section 6 see Metal-mediated Protein Modification) may be relevant to understanding aspects of the evolution of enzymes. Metal-ion mediated redox chemistry with oxygen can modify several amino acids, especially tyrosine, tryptophan, cysteine, and histidine. This may have provided a path to generate new redox cofactors prior to the advent of the complex biosynthetic pathways. 

In summary, a range of oxidative cleavage reactions, catalyzed by dioxygenase enzymes, have been identified, that are involved in catabolic and biosynthetic pathways. While the majority of these enzymes require nonheme iron as cofactor, several examples of copper-dependent or cofactor-independent dioxygenases have come to light, whose mechanisms for oxygen activation and catalytic mechanism share several features with the nonheme iron-dependent dioxygenases. 

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