Heme type monooxygenases

The search for catalysts capable of effecting direct aromatic hydroxylation has been motivated by interest in the modeling of monooxygenase enzymes of both heme and non-heme type [5,6]. The active species in working models may be the hydroxyl radical [7] or oxenoid (oxometal) species [8-10]. 

In any case, biological relevance of superoxoiron(III) complex itself is not straight forward to non heme iron monooxygenase, because this type of complex never shows the reactivity as the monooxygenase does. Thus, superoxoiron(III) species should be not responsible for the enzymatic reaction. 

Some of the major enzyme groups that facilitate this transformation are heme-containing MOs of the cytochrome P450 type [111], alkane hydroxylases, xylene monooxygenases, styrene monooxygenases [105], and haloperoxidases [112],... 

The systems where this type of reaction is produced may be metal-, heme- or flavin-dependent. In flavin-dependent monooxygenases, a flavin-oxygen intermediate reacts with the substrate, producing water in a second step and requiring cofactors for regeneration of the flavin moiety. The non-heme-dependent oxygenases include the... 

Heme coenzymes (8) with redox functions exist in the respiratory chain (see p. 140), in photosynthesis (see p. 128), and in monooxygenases and peroxidases (see p. 24). Heme-containing proteins with redox functions are also referred to as cytochromes. In cytochromes, in contrast to hemoglobin and myoglobin, the iron changes its valence (usually between +2 and +3). There are several classes of heme (a, b, and c), which have different types of substituent - Ri to - R 3. Hemoglobin, myoglobin, and the heme enzymes contain heme b. Two types of heme a are found in cytochrome c oxidase (see p. 132), while heme c mainly occurs in cytochrome c, where it is covalently bound with cysteine residues of the protein part via thioester bonds. 

Since H202 is easier to handle than 02, we will focus on the use of the former. Many metals can be used for this transformation [50]. Among them, iron compounds are of interest as mimics of naturally occurring non-heme catalysts such as methane monooxygenase (MMO) [51a] or the non-heme anti-tumor drug bleomycin [51b]. Epoxidation catalysts should meet several requirements in order to be suitable for this transformation [50]. Most importantly they must activate the oxidant without formation of radicals as this would lead to Fenton-type chemistry and catalyst decomposition. Instead, heterolytic cleavage of the 0—0 bond is desired. In some cases, alkene oxidation furnishes not only epoxides but also diols. The latter transformation will be the topic of the following section. 

How can a simple cofactor, such as heme, give rise to a wide spectrum of protein functionalities While the Fe(III)/Fe(II) couple has a standard redox potential of 0.77 V, when complexed with a protoporphyrin to form free heme, it may decrease to —0.115 V [3-5]. When heme is introduced into a protein matrix, redox potential shows an impressive variation of around 1 V. The electrochemical data for structurally characterized heme proteins involved in electron transfer and redox catalysis has been compiled at the Heme Protein Database (HPD, http //heme.chem. columbia.edu/heme) [6]. The database comprises not only peroxidases but also catalases, oxidases, monooxygenases, and cytochromes. From b-type heme with histidine-tyrosine ligation (E° = 0.55 V) to c-type heme with histidine-methionine... 

Another type of iron-containing monpoxygenase was flrst described by Bernhardt et al. ) and contains a two iron-two-acid-labile-sulfur cluster. It was isolated from bacteria and catalyzes the 0-demethylation of 4-methoxybenzoate The corresponding electron transport chain involves NADH, a flavoprotein and a second iron-sulfur protein It seems that many more bacterial monooxygenases belong to this type rather than to the heme-sulfur-containing category. 

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