Enzymatic hydroxylation of aromatic compounds

Ullrich, René; Hofrichter, Martin

doi:10.1007/s00018-007-6362-1

Cited by 299 publications

(194 citation statements)

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“…30 In the same manner, the oxygenase chemistry described here could alternatively be achieved by use of cytochrome P450s, 96 di-iron hydroxylases, 97 Rieske-type iron-containing oxygenases, 98 pterin-dependent hydroxylases, 99 flavoprotein monooxygenases, 100 and other catalysts. 101 Thus, biochemical and genetic studies will continue to be important to identify the hydroxylases responsible for such transformations in other organisms. General reaction of Fe II /αKG hydroxylases Pyrimidine salvage pathway.…”

Section: Discussionmentioning

confidence: 99%

FeII/α-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism

2008

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Fe II /α-ketoglutarate-dependent hydroxylases uniformly possess a double-stranded β-helix fold with two conserved histidines and one carboxylate coordinating their mononuclear ferrous ions. Oxidative decomposition of the α-keto acid is proposed to generate a ferryl-oxo intermediate capable of hydroxylating unactivated carbon atoms in a myriad of substrates. This perspective focuses on a subgroup of these enzymes that are involved in pyrimidine salvage, purine decomposition, nucleoside and nucleotide hydroxylation, DNA/RNA repair, and chromatin modification. The varied reaction schemes are presented, and selected structural and kinetic information is summarized. IntroductionFerrous ion and α-ketoglutarate (αKG)-dependent dioxygenases comprise an enzyme superfamily with members present in animals, plants, protists, fungi, bacteria and even viruses. Most representatives of this large group of enzymes couple the oxidative decarboxylation of αKG to various hydroxylation reactions ( Fig. 1), but others are capable of catalyzing desaturation, epoxidation, halogenation, ring formation, or ring expansion reactions, which allows them to fill a wide variety of biological roles including antibiotic biosynthesis, hypoxic sensing, DNA repair, and various types of metabolite transformations. [1][2][3] Not surprisingly, the primary substrates also are diverse and include proteins, lipids, nucleic acids, and a myriad of small molecules that can be used for synthesis or undergo degradation.The sequences of Fe II /αKG dioxygenases show little overall identity, yet the diverse reactions all are catalyzed by proteins with the same core fold and use similar chemistries. 4 The hallmark of these enzymes is their use of Fe II to activate molecular oxygen according to a mechanism (Scheme 1) first proposed by Hanauske-Abel and Günzler in 1982 for prolyl 4-hydroxylase. 5 (A) In the absence of substrates, a "facial triad" (usually two His plus one Asp or Glu occurring in a His-X-Asp/Glu-X n -His motif) weakly bind one face of the hexacoordinate metal. 6,7 (B) The αKG co-substrate displaces two waters and coordinates Fe II in a bidentate fashion with its C1 carboxyl and C2 keto oxygens. The binding of αKG is Correspondence to: Robert P. Hausinger, hausinge@msu.edu. NIH Public Access Author ManuscriptDalton Trans. Author manuscript; available in PMC 2010 July 20. This perspective focuses on the modification of nucleobases, nucleosides, nucleotides, and chromatin by the Fe II and αKG dependent hydroxylases (Table 1). We discuss the degradation and salvage of free bases by the fungal enzymes thymine 7-hydroxylase and xanthine hydroxylase. Next, nucleoside hydroxylases are briefly described. We then examine the developmental modification of DNA in kinetoplastid protozoans and summarize evidence that the JBP1 and JBP2 proteins possess thymidine hydroxylase activity. The oxidative repair of DNA by Escherichia coli AlkB is discussed, and the properties of mammalian homologues are summarized. Finally, we present emerging evidence pointing to...

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Section: Discussionmentioning

confidence: 99%

FeII/α-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism

2008

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“…Accordingly, the manufacturing of 1-naphthol by enzymes should ideally take place in one-pot under mild conditions (room temperature, atmospheric pressure and nearly aqueous solution with small amounts of organic co-solvents), while also reducing the energy required and the noxious waste products resulting from chemical synthesis. [8][9][10][11] To date, most studies into the biocatalytic synthesis of 1-naphthol have focused on monooxygenases. In particular, over the years P450 monooxygenases have been designed for different purposes, from the selective hydroxylation of alkanes (including terminal hydroxylation) to the non-natural olefin cyclopropanation by carbene transfer.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of 1‐Naphthol by a Natural Peroxygenase Engineered by Directed Evolution

et al. 2016

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Abstract:There is an increasing interest in enzymes that catalyze the hydroxylation of naphthalene under mild conditions and with minimal requirements. To address this challenge, an extracellular fungal aromatic peroxygenase with mono(per)oxygenase activity was engineered to selectively convert naphthalene into 1-naphthol. Mutant libraries constructed by random mutagenesis and DNA recombination were screened for peroxygenase activity on naphthalene while quenching the undesired peroxidative activity on 1-naphthol (one-electron oxidation). The resulting double mutant (G241D-R257K) of this process was characterized biochemically and computationally. The conformational changes produced by directed evolution improved the substrate´s catalytic position. Powered exclusively by catalytic concentrations of H2O2, this soluble and stable biocatalyst has total turnover numbers of 50,000, with high regioselectivity (97%) and reduced peroxidative activity.

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“…[3,4] Representing ab iocatalytic alternative to asymmetricd ihydroxylation with toxic transition-metal catalysts, ROs also exhibit ab road substrate scope. [5] Over 300 diverse substrates ranging from polyaromatic hydrocarbons such as phenanthracene to halogenated ethylenes and flavonoid structures were reportedt ob eh ydroxylated with these enzymes. [6,7] Furthermore, ROs were shown to be suitable for bioremediation applications and to have the ability to process xenobiotics.…”

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confidence: 99%

Semirational Engineering of the Naphthalene Dioxygenase from Pseudomonas sp. NCIB 9816‐4 towards Selective Asymmetric Dihydroxylation

2017

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Enzyme-catalyzed asymmetric dihydroxylation is ap owerful tool fort he selective oxyfunctionalization of various organic compounds. By applying Rieske non-heme dioxygenases (ROs), molecular oxygen and ar eduction equivalent are needed for the generation of vicinal cis-diols. We report ac omprehensive mutagenesis study of the active site of the naphthalene dioxygenasef rom Pseudomonas sp. NCIB 9816-4 comprising 62 variants. We aimed to understand the important structure-function relationships by investigating different substituted arene substrates and the geometry of the active site. Introducing single-point mutations at positions F202, A206, V260, H295, F352, and L307 resulted in drastic shifts in the reactions pecificity,r egioselectivity,a nd stereoselectivity (! 90 %) while maintaining the residual activity towards the natural substrate naphthalene.One of the key reactions in chemistryi st he selective oxyfunctionalization of organic compounds. In this context, chiralv icinal 1,2-diols are of particular interest and are often applied as chiral ligands, auxiliaries, and chiral synthons for pharmaceuticals and agrochemicals.[1] These functionalized compounds are generated by multicomponent Rieske non-heme dioxygenases (ROs), which, analogously to some P450sm onooxygenases, consist of ar eductase, af erredoxin, andahexameric oxygenase.[2] In ROs, categorized as types III and IV,t he reductase obtains electrons from the naturalc osubstrate NAD(P)H,a nd a ferredoxin component shuttles electrons from the reductase to the oxygenase active site, at which actual oxygen activation and substrate hydroxylation occur. [3,4] Representing ab iocatalytic alternative to asymmetricd ihydroxylation with toxic transition-metal catalysts, ROs also exhibit ab road substrate scope.[5] Over 300 diverse substrates ranging from polyaromatic hydrocarbons such as phenanthracene to halogenated ethylenes and flavonoid structures were reportedt ob eh ydroxylated with these enzymes. [6,7] Furthermore, ROs were shown to be suitable for bioremediation applications and to have the ability to process xenobiotics. [8,9] In industry, ROs are utilized to manufacture the blue dye indigo, which is crucial for the production of denim cloth.[10]Oxygen-dependent ROsn ot only convert ah uge variety of compounds, but these catalysts also displayabroad reaction scope. With these enzymes ystems it is possible to address monohydroxylations( Scheme 1, path I), dihydroxylations (Scheme 1, path II), and O-dealkylations (Scheme 1, path III) with high regio-a nd stereoselectivities. [11,12] Recently,s emirational engineering of the cumene dioxygenase (CDO) from Pseudomonas fluorescens IP01 expanded the substrate scope of these versatile catalysts to ar ange of sterically demanding cyclic and linear alkenesa nd monoterpenes. The CDOs ingle variant M232Aw as able to convert different terpeneg eometries such as myrcene and (À)-a-pinene with high specificity and selectivity. [13] This work motivated us to gain furtheri nsighti nto crucial structure-function relation...

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Enzymatic hydroxylation of aromatic compounds

Cited by 299 publications

References 219 publications

FeII/α-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism

FeII/α-ketoglutarate hydroxylases involved in nucleobase, nucleoside, nucleotide, and chromatin metabolism

Synthesis of 1‐Naphthol by a Natural Peroxygenase Engineered by Directed Evolution

Semirational Engineering of the Naphthalene Dioxygenase from Pseudomonas sp. NCIB 9816‐4 towards Selective Asymmetric Dihydroxylation

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