Heme-thiolate ferryl of aromatic peroxygenase is basic and reactive

Wang, Xiaoshi; Ullrich, René; Hofrichter, Martin; Groves, John T.

doi:10.1073/pnas.1503340112

Cited by 80 publications

(63 citation statements)

References 50 publications

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“…6A. The optical spectrum of Int-2 has characteristics that are highly similar to those reported for protonated thiolate Fe 4+ hydroxide complexes prepared in P450 (44) and the thiolateligated heme peroxygenase APO (45). Notably, Int-2 is characterized by a Soret maximum at λ max = 426 nm that is clearly redshifted and has a lower molar extinction coefficient relative to the Fe 3+ −OH 2 form of the enzyme.…”

Section: Significancesupporting

confidence: 67%

See 1 more Smart Citation

Catalytic strategy for carbon−carbon bond scission by the cytochrome P450 OleT

Grant

Mitchell

Makris

2016

Proc. Natl. Acad. Sci. U.S.A.

102

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OleT is a cytochrome P450 that catalyzes the hydrogen peroxidedependent metabolism of C n chain-length fatty acids to synthesize C n-1 1-alkenes. The decarboxylation reaction provides a route for the production of drop-in hydrocarbon fuels from a renewable and abundant natural resource. This transformation is highly unusual for a P450, which typically uses an Fe 4+ −oxo intermediate known as compound I for the insertion of oxygen into organic substrates. OleT, previously shown to form compound I, catalyzes a different reaction. A large substrate kinetic isotope effect (≥8) for OleT compound I decay confirms that, like monooxygenation, alkene formation is initiated by substrate C−H bond abstraction. Rather than finalizing the reaction through rapid oxygen rebound, alkene synthesis proceeds through the formation of a reaction cycle intermediate with kinetics, optical properties, and reactivity indicative of an Fe 4+ −OH species, compound II. The direct observation of this intermediate, normally fleeting in hydroxylases, provides a rationale for the carbon−carbon scission reaction catalyzed by OleT.C ytochrome P450 (CYP) enzymes catalyze an extraordinary breadth of physiologically important oxidations for xenobiotic detoxification and specialized biosynthetic pathways (1, 2). The metabolic diversity of CYP enzymes originates from a sophisticated interplay of substrate molecular recognition with precise tuning of metal oxygen species formed at the enzyme active site. CYPs use a thiolate-ligated heme iron cofactor to activate molecular oxygen and produce short-lived ferric superoxo (3-5), ferric (hydro)peroxo (6-8), and ferryl (9, 10) intermediates. Coordinated efforts over several decades have resulted in isolation of each intermediate, including recent characterization of the principal oxidant thought to be responsible for the vast majority of P450 oxidations, the Fe 4+ −oxo pi−cation radical species commonly referred to as compound I (or P450-I) (10).The archetypal P450 hydroxylation involves C−H bond abstraction by P450-I and ensuing rapid oxygen insertion through a recombination process termed "oxygen rebound" (11, 12). The hydrogen abstraction/rebound mechanism describes the strategy used for most P450 transformations, and is thought to describe catalysis by numerous metal-dependent oxygenases and synthetic bio-inspired metal−oxo complexes (e.g., refs. 13-17). Despite the ubiquity of this mechanism, in some metalloenzymes, a metal−oxo species is formed that is not ultimately destined for incorporation into a substrate. Some characterized examples include the nonheme dinuclear iron ribonucleotide reductase (RNR R2) (18,19) and mononuclear iron halogenase SyrB2 (20-22). The mechanisms for RNR and SyrB2 highlight the importance of quaternary structural elements, an extensive 35-Å proton-coupled electron transfer pathway in RNR (23), and extremely subtle (subangstrom) substrate positional tuning (SyrB2) (21,22), to enable efficient circumvention from the monooxygenation reaction coordinate.P450-I has also been link...

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Section: Significancesupporting

confidence: 67%

“…Thiolate-ligated compound II species, including that of chloroperoxidase (CPO-II) (46) and aromatic peroxygenase (APO-II) (45), are able to oxidize phenols, albeit with variable proficiency. Int-2 was first prepared by mixing the EA-H 39 -bound enzyme with H 2 O 2 to favor the rapid depletion of Ole-I and formation of Int-2.…”

Section: Significancementioning

confidence: 99%

Catalytic strategy for carbon−carbon bond scission by the cytochrome P450 OleT

Grant

Mitchell

Makris

2016

Proc. Natl. Acad. Sci. U.S.A.

102

View full text Add to dashboard Cite

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“…This pattern of unprotonated/protonated ferryl in Compound I/II in P450 is mirrored in both APO and chloroperoxidase2425 (Fig. 3).…”

Section: Discussionmentioning

confidence: 82%

Direct visualization of a Fe(IV)–OH intermediate in a heme enzyme

et al. 2016

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Catalytic heme enzymes carry out a wide range of oxidations in biology. They have in common a mechanism that requires formation of highly oxidized ferryl intermediates. It is these ferryl intermediates that provide the catalytic engine to drive the biological activity. Unravelling the nature of the ferryl species is of fundamental and widespread importance. The essential question is whether the ferryl is best described as a Fe(IV)=O or a Fe(IV)–OH species, but previous spectroscopic and X-ray crystallographic studies have not been able to unambiguously differentiate between the two species. Here we use a different approach. We report a neutron crystal structure of the ferryl intermediate in Compound II of a heme peroxidase; the structure allows the protonation states of the ferryl heme to be directly observed. This, together with pre-steady state kinetic analyses, electron paramagnetic resonance spectroscopy and single crystal X-ray fluorescence, identifies a Fe(IV)–OH species as the reactive intermediate. The structure establishes a precedent for the formation of Fe(IV)–OH in a peroxidase.

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“…Strikingly, Sun and co-workersr eported am ononuclear ruthenium catalyst, with an activity competitive with that of the OEC, with a TOF of 100 s À1 and aT ON of 10 6 . [34] In addition, molecular catalysts based on iridium [35][36][37][38][39] and the earth-abundant first-row transition elements vanadium, [40] manganese, [41][42][43][44][45][46][47] iron, [48][49][50][51] copper, [52][53][54][55][56][57][58] nickel, [59][60][61][62][63][64] and copper [65][66][67][68][69][70] have also been described.…”

Section: Introductionmentioning

confidence: 99%

Quantum Chemical Modeling of Homogeneous Water Oxidation Catalysis

Liao

Siegbahn

2017

ChemSusChem

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The design of efficient and robust water oxidation catalysts has proven challenging in the development of artificial photosynthetic systems for solar energy harnessing and storage. Tremendous progress has been made in the development of homogeneous transition‐metal complexes capable of mediating water oxidation. To improve the efficiency of the catalyst and to design new catalysts, a detailed mechanistic understanding is necessary. Quantum chemical modeling calculations have been successfully used to complement the experimental techniques to suggest a catalytic mechanism and identify all stationary points, including transition states for both O−O bond formation and O2 release. In this review, recent progress in the applications of quantum chemical methods for the modeling of homogeneous water oxidation catalysis, covering various transition metals, including manganese, iron, cobalt, nickel, copper, ruthenium, and iridium, is discussed.

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Heme-thiolate ferryl of aromatic peroxygenase is basic and reactive

Cited by 80 publications

References 50 publications

Catalytic strategy for carbon−carbon bond scission by the cytochrome P450 OleT

Catalytic strategy for carbon−carbon bond scission by the cytochrome P450 OleT

Direct visualization of a Fe(IV)–OH intermediate in a heme enzyme

Quantum Chemical Modeling of Homogeneous Water Oxidation Catalysis

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