Oxygen insertion enzymes

It has been reported that cyclohexanone monooxygenase displays a broad substrate specificity for cyclic ketones38. Moreover, the lactonization of 2-methylcyclohexanone (3), catalyzed by this enzyme, exhibits a regioselectivity comparable with that found for the chemical Baeyer Villiger oxidation oxygen insertion only takes place between the carbonyl group and the substituted carbon center393. 

Enzymes have evolved to couple efficiently the reduction of dioxygen to the oxidation of biological compounds. Difficult C-H abstraction and O-atom insertion reactions are catalyzed by oxygen-activating enzymes under mild conditions and with high specificity. 

The exact mechanistic details of oxygen insertion into the C-H bond are still the subject of intense discussion. One of the most popular proposals appears to be that of the so-called rebound mechanism , which proceeds by an initial hydrogen abstraction from the alkane (RH) by the active oxygen intermediate to form a radical R and a hydroxo-iron species as intermediates. The radical then rebounds on the hydroxy group and generates the enzyme-product species[29). Alternative proposals involve cationic intermediates1301 or two-state reactivity with multiple electromer species for epoxidations131. ... 

With carbon-carbon triple bonds, oxygen insertion yields an oxirene which opens by heterolytic C — O bond cleavage to form a highly reactive intermediate which binds covalently to the enzyme. In the case of 17a-ethynyl steroids, the reaction can also result in an extension of ring D (Fig. 31.12). 

B-deoxyrifamycin 5, suggests that elimination of C-34a in the protorifamycin I to 8-deoxyrifamycin 5 bioconversion also occurs by oxidation and decarboxylation, as seen above for the rifamycin W to rifamycin 5 conversion the enzymes for elimination of C-34a, for ring extension by oxygen insertion between C-12 and C-29, and for formation of the five-membered ring in the chromophore thus seem to accept either 8-deoxy or B-hydroxy substrates. 

The enzymes which achieve geometrically controlled attack on unactivated hydrogens do not use chlorine atoms for the attack, but instead perform oxygen insertions. They have iron-porphyrin units and are members of a group generally described as cytochromes P-450, named for a particular spectroscopic band. These enzymes have been the subject of very intensive biochemical and model studies. 

As described in 3.1.1, various types of catecholatoiron model complexes in the form of the chelate coordination have been isolated and found to give the oxygen insertion products by the reaction with molecular oxygen. Different from the enzyme structure, however, most of them are in the six-coordinate configuration. 

The product (6 hexanohde) is a cyclic ester or lactone (Section 19 15) Like the Baeyer-Vilhger oxidation an oxygen atom is inserted between the carbonyl group and a carbon attached to it But peroxy acids are not involved m any way the oxidation of cyclohexanone is catalyzed by an enzyme called cyclohexanone monooxygenase with the aid of certain coenzymes... 

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