Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2

Shaun D. Wong, Martin Srnec, Megan L. Matthews, Lei V. Liu, Yeonju Kwak, Kiyoung Park, Caleb B. Bell, E. Ercan Alp, Jiyong Zhao, Yoshitaka Yoda, Shinji Kitao, Makoto Seto, Carsten Krebs, Joseph M. Bollinger, Jr., Edward I. Solomon

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Abstract

Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(iv)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(iv)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(iv)=O active site. Here we present NRVS structural characterization of the reactive Fe(iv)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(iv)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.

Original languageEnglish (US)
Pages (from-to)320-323
Number of pages4
JournalNature
Volume499
Issue number7458
DOIs
StatePublished - Jul 26 2013

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Halogenation
Enzymes
Hydroxylation
Spectrum Analysis
Pseudomonas syringae
Biological Phenomena
Synchrotrons
Phenylalanine
Neurotransmitter Agents
syringomycin
Hydrogen
Catalytic Domain
Iron
Bacteria

All Science Journal Classification (ASJC) codes

  • General

Cite this

Wong, S. D., Srnec, M., Matthews, M. L., Liu, L. V., Kwak, Y., Park, K., ... Solomon, E. I. (2013). Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2. Nature, 499(7458), 320-323. https://doi.org/10.1038/nature12304
Wong, Shaun D. ; Srnec, Martin ; Matthews, Megan L. ; Liu, Lei V. ; Kwak, Yeonju ; Park, Kiyoung ; Bell, Caleb B. ; Alp, E. Ercan ; Zhao, Jiyong ; Yoda, Yoshitaka ; Kitao, Shinji ; Seto, Makoto ; Krebs, Carsten ; Bollinger, Jr., Joseph M. ; Solomon, Edward I. / Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2. In: Nature. 2013 ; Vol. 499, No. 7458. pp. 320-323.
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abstract = "Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(iv)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(iv)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(iv)=O active site. Here we present NRVS structural characterization of the reactive Fe(iv)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(iv)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.",
author = "Wong, {Shaun D.} and Martin Srnec and Matthews, {Megan L.} and Liu, {Lei V.} and Yeonju Kwak and Kiyoung Park and Bell, {Caleb B.} and Alp, {E. Ercan} and Jiyong Zhao and Yoshitaka Yoda and Shinji Kitao and Makoto Seto and Carsten Krebs and {Bollinger, Jr.}, {Joseph M.} and Solomon, {Edward I.}",
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Wong, SD, Srnec, M, Matthews, ML, Liu, LV, Kwak, Y, Park, K, Bell, CB, Alp, EE, Zhao, J, Yoda, Y, Kitao, S, Seto, M, Krebs, C, Bollinger, Jr., JM & Solomon, EI 2013, 'Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2', Nature, vol. 499, no. 7458, pp. 320-323. https://doi.org/10.1038/nature12304

Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2. / Wong, Shaun D.; Srnec, Martin; Matthews, Megan L.; Liu, Lei V.; Kwak, Yeonju; Park, Kiyoung; Bell, Caleb B.; Alp, E. Ercan; Zhao, Jiyong; Yoda, Yoshitaka; Kitao, Shinji; Seto, Makoto; Krebs, Carsten; Bollinger, Jr., Joseph M.; Solomon, Edward I.

In: Nature, Vol. 499, No. 7458, 26.07.2013, p. 320-323.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2

AU - Wong, Shaun D.

AU - Srnec, Martin

AU - Matthews, Megan L.

AU - Liu, Lei V.

AU - Kwak, Yeonju

AU - Park, Kiyoung

AU - Bell, Caleb B.

AU - Alp, E. Ercan

AU - Zhao, Jiyong

AU - Yoda, Yoshitaka

AU - Kitao, Shinji

AU - Seto, Makoto

AU - Krebs, Carsten

AU - Bollinger, Jr., Joseph M.

AU - Solomon, Edward I.

PY - 2013/7/26

Y1 - 2013/7/26

N2 - Mononuclear non-haem iron (NHFe) enzymes catalyse a broad range of oxidative reactions, including halogenation, hydroxylation, ring closure, desaturation and aromatic ring cleavage reactions. They are involved in a number of biological processes, including phenylalanine metabolism, the production of neurotransmitters, the hypoxic response and the biosynthesis of secondary metabolites. The reactive intermediate in the catalytic cycles of these enzymes is a high-spin S = 2 Fe(iv)=O species, which has been trapped for a number of NHFe enzymes, including the halogenase SyrB2 (syringomycin biosynthesis enzyme 2). Computational studies aimed at understanding the reactivity of this Fe(iv)=O intermediate are limited in applicability owing to the paucity of experimental knowledge about its geometric and electronic structure. Synchrotron-based nuclear resonance vibrational spectroscopy (NRVS) is a sensitive and effective method that defines the dependence of the vibrational modes involving Fe on the nature of the Fe(iv)=O active site. Here we present NRVS structural characterization of the reactive Fe(iv)=O intermediate of a NHFe enzyme, namely the halogenase SyrB2 from the bacterium Pseudomonas syringae pv. syringae. This intermediate reacts via an initial hydrogen-atom abstraction step, performing subsequent halogenation of the native substrate or hydroxylation of non-native substrates. A correlation of the experimental NRVS data to electronic structure calculations indicates that the substrate directs the orientation of the Fe(iv)=O intermediate, presenting specific frontier molecular orbitals that can activate either selective halogenation or hydroxylation.

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Wong SD, Srnec M, Matthews ML, Liu LV, Kwak Y, Park K et al. Elucidation of the Fe(iv)=O intermediate in the catalytic cycle of the halogenase SyrB2. Nature. 2013 Jul 26;499(7458):320-323. https://doi.org/10.1038/nature12304