Sequenzielle enzymatische Oxidation von Aminoarenen zu Nitroarenen über Hydroxylamine

Winkler, Robert; Hertweck, Christian

doi:10.1002/ange.200500365

Cited by 24 publications

(9 citation statements)

References 36 publications

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“…Also being a member of the large fourhelix bundle protein family, AurF catalyzes the N-oxygenation of p-aminobenzoic acid to p-nitrobenzoic acid during the biosynthesis of the nitroaryl-substituted metabolite aureothin in S. thioluteus bacteria (Scheme 2). [13] Despite the fact that the activity of isolated AurF has been assessed up to now by using H 2 O 2 as the oxidizing agent, it is expected that the enzyme uses molecular oxygen under native conditions. [14] Similar to the R2 subunit of Chlamydia ribonucleotide reductases, it was originally assumed on the basis of sequence homologies that the new N-oxygenase AurF of S. thioluteus is a carboxylate-bridged diiron protein.…”

Section: Methodsmentioning

confidence: 99%

Carboxylate‐Bridged Dinuclear Active Sites in Oxygenases: Diiron, Dimanganese, or is Heterodinuclear Better?

Roth¹,

Plass²

2008

Angew Chem Int Ed

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bioinorganic chemistry · enzymes · iron · manganese · metalloproteinsCarboxylate-bridged diiron centers are a frequently observed structural motif in biological systems, and the corresponding enzymes catalyze a wide range of important reactions. Within this class of enzymes, a highly interesting family of diiron proteins is characterized by an eye-catching feature in their secondary structure: The dinuclear metal site is localized between a bundle of four a helices (four-helix bundle proteins) that provide coordinating amino acid residues (histidine, glutamate, and/or aspartate) for the binding of metal ions, which are usually bridged by proteinbased carboxylate functionalities and/or oxo ligands (water molecules, hydroxo or oxo ions). It is particularly interesting that the members of this protein family, despite their similarly structured metal sites, catalyze a wide variety of biological processes that appear at first sight to be highly different. However, a closer look at the reactions reveals that most of these processes are based on the common reactivity of the enzymes towards molecular oxygen, which is activated and reduced by the dinuclear metal site. Fascinating and intensely studied examples of this family are the soluble methane monooxygenases (sMMOs), [1] the soluble fatty acid desaturases, [2] and the ribonucleotide reductases (RNRs; Scheme 1). [3] The similar reactivity towards oxygen, the highly conserved structure of the dinuclear metal site, and a protein environment with four-helix bundles has led to the belief that this family of enzymes has evolved from a common ancient primitive oxidase. The original task of this oxidase might have been the fast and reliable reduction of molecular oxygen, thus protecting the cell against oxidative stress caused by the transition from a reducing to an oxidizing atmosphere about 2.5 billion years ago. This hypothesis is supported by a recent study in which the replacement of a single amino acid in a soluble fatty acid desaturase led to a total loss of desaturase acitivity and a simultaneous increase in oxidase activity. [4] Very recently, two new members of this protein family were isolated from certain bacteria and found to be quite different from their prominent relatives in various aspects. These unusual enzymes are the ribonucleotide reductase of Chlamydia trachomatis [5] and the N-oxygenase AurF of Streptomyces thioluteus.[6] Interestingly, the unambiguous assignment of the identity of the active metal sites in these systems still remains an open question. In particular, it is not yet entirely clear whether these enzymes are homometallic diiron or dimanganese systems or even contain heterometallic MnFe centers as their active sites. The elucidation of the chemical identity and reactivity of these dinuclear metal sites represents a highly exciting and challenging task in the field of modern bioinorganic chemistry.It is believed that the deoxygenation of ribonucleotides catalyzed by ribonucleotide reductases is initiated by the formation of a protein-based t...

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Section: Methodsmentioning

confidence: 99%

Carboxylate‐Bridged Dinuclear Active Sites in Oxygenases: Diiron, Dimanganese, or is Heterodinuclear Better?

Roth¹,

Plass²

2008

Angew Chem Int Ed

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“…[8] Herein we present the coordination sphere and catalyst geometry of the first reported Mndependent monooxygenase, the N-oxygenase AurF from Streptomyces thioluteus. [9][10][11][12] Recently we showed that AurF is able to selectively oxidize p-aryl amino groups to the corresponding nitro groups (Scheme 1). The enzyme can be applied in various ways-in vivo, in vitro, and immobilized in flow driven by H 2 O 2 -highlighting its potential application as a biocatalyst.…”

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confidence: 99%

A Binuclear Manganese Cluster That Catalyzes Radical‐Mediated N‐Oxygenation

et al. 2007

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“…[11,12] Nevertheless, it has been demonstrated for two structurally related dioxygenases that oxygen activation can be achieved by either metal. [13] What is quite striking is that the aureothin biosynthesis gene cluster does not contain any gene coding for components of an electron transfer chain, which usually consists of a ferredoxin, a ferredoxin reductase and NAD(P)H. [14] However, AurF has been proven to be active in vivo in at least three different organisms: in its natural host Streptomyces thioluteus, [15] as well as in the heterologous hosts Streptomyces lividans [7] and E. coli. [4] Moreover, the purified enzyme can be regenerated in vitro by using the peroxide shunt.…”

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confidence: 97%

“…[6] Through a number of in vivo and in vitro studies, we could show that Noxygenation of the amino substrates occurs stepwise and involves hydroxylamine and nitroso intermediates. [7] Furthermore, we could prove the participation of manganese in the catalytic action of AurF and were able to present the first X-ray structure of an N-oxygenase. [8,9] Later, another group reported the crystal structure of an iron-containing variant of AurF.…”

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confidence: 98%

A Ribonucleotide Reductase‐Like Electron Transfer System in the Nitroaryl‐Forming N‐Oxygenase AurF

et al. 2011

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Sequenzielle enzymatische Oxidation von Aminoarenen zu Nitroarenen über Hydroxylamine

Cited by 24 publications

References 36 publications

Carboxylate‐Bridged Dinuclear Active Sites in Oxygenases: Diiron, Dimanganese, or is Heterodinuclear Better?

Carboxylate‐Bridged Dinuclear Active Sites in Oxygenases: Diiron, Dimanganese, or is Heterodinuclear Better?

A Binuclear Manganese Cluster That Catalyzes Radical‐Mediated N‐Oxygenation

A Ribonucleotide Reductase‐Like Electron Transfer System in the Nitroaryl‐Forming N‐Oxygenase AurF

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