Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase

Chen Wang, Wei Chen Chang, Yisong Guo, Hui Huang, Spencer C. Peck, Maria E. Pandelia, Geng Min Lin, Hung Wen Liu, Carsten Krebs, Joseph M. Bollinger, Jr.

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1- phosphonate (S-HPP) to the antibiotic fosfomycin [(1R,2S)- epoxypropylphosphonate] in an unusual 1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been classified as an oxidase, with proposed mechanisms differing primarily in the identity of the O2-derived iron complex that abstracts hydrogen (H•) from C1 of S-HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate is actually H2O 2 and that HppE therefore almost certainly uses an iron(IV)-oxo complex as the H• abstractor. Reaction with H2O2 is accelerated by bound substrate and produces fosfomycin catalytically with a stoichiometry of unity. The ability of catalase to suppress the HppE activity previously attributed to its direct utilization of O2 implies that reduction of O2 and utilization of the resultant H2O 2 were actually operant.

Original languageEnglish (US)
Pages (from-to)991-995
Number of pages5
JournalScience
Volume342
Issue number6161
DOIs
StatePublished - Jan 1 2013

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Fosfomycin
Organophosphonates
Epoxy Compounds
Peroxidase
Iron
Catalase
Hydrogen
Oxidoreductases
Alcohols
Anti-Bacterial Agents
epoxidase
ferryl iron

All Science Journal Classification (ASJC) codes

  • Medicine(all)
  • General

Cite this

Wang, Chen ; Chang, Wei Chen ; Guo, Yisong ; Huang, Hui ; Peck, Spencer C. ; Pandelia, Maria E. ; Lin, Geng Min ; Liu, Hung Wen ; Krebs, Carsten ; Bollinger, Jr., Joseph M. / Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. In: Science. 2013 ; Vol. 342, No. 6161. pp. 991-995.
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abstract = "The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1- phosphonate (S-HPP) to the antibiotic fosfomycin [(1R,2S)- epoxypropylphosphonate] in an unusual 1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been classified as an oxidase, with proposed mechanisms differing primarily in the identity of the O2-derived iron complex that abstracts hydrogen (H•) from C1 of S-HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate is actually H2O 2 and that HppE therefore almost certainly uses an iron(IV)-oxo complex as the H• abstractor. Reaction with H2O2 is accelerated by bound substrate and produces fosfomycin catalytically with a stoichiometry of unity. The ability of catalase to suppress the HppE activity previously attributed to its direct utilization of O2 implies that reduction of O2 and utilization of the resultant H2O 2 were actually operant.",
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Wang, C, Chang, WC, Guo, Y, Huang, H, Peck, SC, Pandelia, ME, Lin, GM, Liu, HW, Krebs, C & Bollinger, Jr., JM 2013, 'Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase', Science, vol. 342, no. 6161, pp. 991-995. https://doi.org/10.1126/science.1240373

Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. / Wang, Chen; Chang, Wei Chen; Guo, Yisong; Huang, Hui; Peck, Spencer C.; Pandelia, Maria E.; Lin, Geng Min; Liu, Hung Wen; Krebs, Carsten; Bollinger, Jr., Joseph M.

In: Science, Vol. 342, No. 6161, 01.01.2013, p. 991-995.

Research output: Contribution to journalArticle

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AU - Chang, Wei Chen

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AU - Huang, Hui

AU - Peck, Spencer C.

AU - Pandelia, Maria E.

AU - Lin, Geng Min

AU - Liu, Hung Wen

AU - Krebs, Carsten

AU - Bollinger, Jr., Joseph M.

PY - 2013/1/1

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N2 - The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1- phosphonate (S-HPP) to the antibiotic fosfomycin [(1R,2S)- epoxypropylphosphonate] in an unusual 1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been classified as an oxidase, with proposed mechanisms differing primarily in the identity of the O2-derived iron complex that abstracts hydrogen (H•) from C1 of S-HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate is actually H2O 2 and that HppE therefore almost certainly uses an iron(IV)-oxo complex as the H• abstractor. Reaction with H2O2 is accelerated by bound substrate and produces fosfomycin catalytically with a stoichiometry of unity. The ability of catalase to suppress the HppE activity previously attributed to its direct utilization of O2 implies that reduction of O2 and utilization of the resultant H2O 2 were actually operant.

AB - The iron-dependent epoxidase HppE converts (S)-2-hydroxypropyl-1- phosphonate (S-HPP) to the antibiotic fosfomycin [(1R,2S)- epoxypropylphosphonate] in an unusual 1,3-dehydrogenation of a secondary alcohol to an epoxide. HppE has been classified as an oxidase, with proposed mechanisms differing primarily in the identity of the O2-derived iron complex that abstracts hydrogen (H•) from C1 of S-HPP to initiate epoxide ring closure. We show here that the preferred cosubstrate is actually H2O 2 and that HppE therefore almost certainly uses an iron(IV)-oxo complex as the H• abstractor. Reaction with H2O2 is accelerated by bound substrate and produces fosfomycin catalytically with a stoichiometry of unity. The ability of catalase to suppress the HppE activity previously attributed to its direct utilization of O2 implies that reduction of O2 and utilization of the resultant H2O 2 were actually operant.

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Wang C, Chang WC, Guo Y, Huang H, Peck SC, Pandelia ME et al. Evidence that the fosfomycin-producing epoxidase, HppE, is a non-heme-iron peroxidase. Science. 2013 Jan 1;342(6161):991-995. https://doi.org/10.1126/science.1240373