Enzyme monooxygenases

Oxepin and its derivatives have attracted attention for several reasons. Oxepin is closely related to cycloheptatriene and its aza analog azepine and it is a potential antiaromatic system with 871-elcctrons. Oxepin can undergo valence isomerization to benzene oxide, and the isomeric benzene oxide is the first step in the metabolic oxidation of aromatic compounds by the enzyme monooxygenase. 

One-step hydroxylation of aromatic nucleus with nitrous oxide (N2O) is among recently discovered organic reactions. A high eflSciency of FeZSM-5 zeolites in this reaction relates to a pronounced biomimetic-type activity of iron complexes stabilized in ZSM-5 matrix. N2O decomposition on these complexes produces particular atomic oj gen form (a-oxygen), whose chemistry is similar to that performed by the active oxygen of enzyme monooxygenases. Room temperature oxidation reactions of a-oxygen as well as the data on the kinetic isotope effect and Moessbauer spectroscopy show FeZSM-5 zeolite to be a successfiil biomimetic model. 

Tsuji and coworkers reported that copper(I) chloride in the presence of pyridine, methanol and dioxygen promotes the stoichiometric oxidation of pyrocatechol to methyl muconate.606 Labeling lg02 studies have shown that only one atom of the dioxygen molecule is incorporated in the substrate, while the other one is transformed into water as in enzymic monooxygenases (equation 275)607 (and not as in dioxygenases, viz. pyrocatechase). This reaction has been shown by Rogic et al. to proceed via two steps (equation 276).580,58 ... 

The metabolism of cholesterol involves modifications to the alkyl side chain and the introduction of substituents onto the phenanthrene ring. A group of enzymes, monooxygenases, plays an important role in catalyzing the formation of bile salts in the liver and steroid hormones in the adrenal gland... 

Oil-eating bacteria can oxidize long-chain alkanes. In the first step of the pathway, the enzyme monooxygenase catalyzes a reaction that converts the long-chain alkane into a primary alcohol. Data from research studies indicate that three more reactions are required to allow the primary alcohol to enter the p-oxidation pathway. Propose a pathway that would convert the long-chain alcohol into a product that could enter the p-oxidation pathway. 

Oxidations/hydroxylations of linactivated saturated carbons (polyunsaturated) fatty acids epoxidation and dihydroxylation of alkenes aromatic compounds (- unsaturated diols) hydroxylated compounds and aldehydes diols (and lactonization) enzyme catalyzed Baeyer-Villiger oxidations organic sulfides (sulfoxidation) Be, Mi, Mp, Po, Ra, CytP450 enzymes, monooxygenases SLO An, Nc, Po Pp (mutant strain), Ce Go, Ps Bp, Go, Ko, Ps, HLADH Ac, Ps, CHO BY, An, Ceq, Mi, Po, CPO, BSA... 

Kerosene fuel contains approximately 57% alkanes. Alkanes with 10 to 22 carbon unit chains are the most easily utilized hydrocarbons. These alkanes are oxidized via the enzyme monooxygenase to yield the corresponding alcohol. This oxidation can be terminal or subterminal. With an attack at the terminal carbon, the hydrocarbon is converted directly to the primary alcohol. Some microorganisms will degrade hydrocarbons at a subterminal carbon, converting the hydrocarbon first to a secondary alcohol that is then further oxidized to a ketone and ester (Wyatt, 1984 Bartha and Atlas, 1987). The ester is finally hydrolyzed to form an acid and the primary alcohol. 

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... 

Organic chemists often use enantiomencally homogeneous starting materials for the synthe SIS of complex molecules (see Chiral Drugs p 296) A novel preparation of the S enantiomer of compound B has been descnbed using a bacterial cyclohexanone monooxygenase enzyme system... 

In one study, a coarse-grained sand aquifer was injected with methane and oxygen to stimulate the production of methane monooxygenase (MMO) enzyme which is capable of degrading TCE (18). TCE, added at 60—100 )-lg/L, was degraded by 20—30%. Injected concentrations of methane and oxygen were approximately 20 mg/L and 32 mg/L, respectively. 

In the endoplasmic reticulum of eukaryotic cells, the oxidation of the terminal carbon of a normal fatty acid—a process termed ch-oxidation—can lead to the synthesis of small amounts of dicarboxylic acids (Figure 24.27). Cytochrome P-450, a monooxygenase enzyme that requires NADPH as a coenzyme and uses O, as a substrate, places a hydroxyl group at the terminal carbon. Subsequent oxidation to a carboxyl group produces a dicarboxylic acid. Either end can form an ester linkage to CoA and be subjected to /3-oxidation, producing a... 

Squalene monooxygenase, an enzyme bound to the endoplasmic reticulum, converts squalene to squalene-2,3-epoxide (Figure 25.35). This reaction employs FAD and NADPH as coenzymes and requires Og as well as a cytosolic protein called soluble protein activator. A second ER membrane enzyme, 2,3-oxidosqualene lanosterol cyclase, catalyzes the second reaction, which involves a succession of 1,2 shifts of hydride ions and methyl groups. 

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. 

Cytochrome P450 monooxygenases are characterized through the presence of the heme (protoporphyrin IX) prosthetic group (Scheme 10.1) that is coordinated to the enzyme through a conserved cysteine ligand. They have obtained their name from the signature absorption band with a maximum near 450 nm in the difference spectrum when incubated with CO. The absorption arises from the Soret Jilt transition of the ferrous protoporphyrin IX-CO complex. 

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