O-H activation by an unexpected ferryl intermediate during catalysis by 2-hydroxyethylphosphonate dioxygenase

Spencer C. Peck, Chen Wang, Laura M.K. Dassama, Bo Zhang, Yisong Guo, Lauren J. Rajakovich, Joseph M. Bollinger, Jr., Carsten Krebs, Wilfred A. Van Der Donk

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Activation of O-H bonds by inorganic metal-oxo complexes has been documented, but no cognate enzymatic process is known. Our mechanistic analysis of 2-hydroxyethylphosphonate dioxygenase (HEPD), which cleaves the C1-C2 bond of its substrate to afford hydroxymethylphosphonate on the biosynthetic pathway to the commercial herbicide phosphinothricin, uncovered an example of such an O-H-bond-cleavage event. Stopped-flow UV-visible absorption and freeze-quench Mössbauer experiments identified a transient iron(IV)-oxo (ferryl) complex. Maximal accumulation of the intermediate required both the presence of deuterium in the substrate and, importantly, the use of 2H2O as solvent. The ferryl complex forms and decays rapidly enough to be on the catalytic pathway. To account for these unanticipated results, a new mechanism that involves activation of an O-H bond by the ferryl complex is proposed. This mechanism accommodates all available data on the HEPD reaction.

Original languageEnglish (US)
Pages (from-to)2045-2052
Number of pages8
JournalJournal of the American Chemical Society
Volume139
Issue number5
DOIs
StatePublished - Feb 8 2017

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Dioxygenases
Catalysis
Chemical activation
Deuterium
Herbicides
Coordination Complexes
Biosynthetic Pathways
Substrates
Metals
Iron
Experiments
2-hydroxyethyl phosphonate
phosphinothricin
hydroxymethylphosphonate
ferryl iron

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Cite this

Peck, S. C., Wang, C., Dassama, L. M. K., Zhang, B., Guo, Y., Rajakovich, L. J., ... Van Der Donk, W. A. (2017). O-H activation by an unexpected ferryl intermediate during catalysis by 2-hydroxyethylphosphonate dioxygenase. Journal of the American Chemical Society, 139(5), 2045-2052. https://doi.org/10.1021/jacs.6b12147
Peck, Spencer C. ; Wang, Chen ; Dassama, Laura M.K. ; Zhang, Bo ; Guo, Yisong ; Rajakovich, Lauren J. ; Bollinger, Jr., Joseph M. ; Krebs, Carsten ; Van Der Donk, Wilfred A. / O-H activation by an unexpected ferryl intermediate during catalysis by 2-hydroxyethylphosphonate dioxygenase. In: Journal of the American Chemical Society. 2017 ; Vol. 139, No. 5. pp. 2045-2052.
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O-H activation by an unexpected ferryl intermediate during catalysis by 2-hydroxyethylphosphonate dioxygenase. / Peck, Spencer C.; Wang, Chen; Dassama, Laura M.K.; Zhang, Bo; Guo, Yisong; Rajakovich, Lauren J.; Bollinger, Jr., Joseph M.; Krebs, Carsten; Van Der Donk, Wilfred A.

In: Journal of the American Chemical Society, Vol. 139, No. 5, 08.02.2017, p. 2045-2052.

Research output: Contribution to journalArticle

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AU - Peck, Spencer C.

AU - Wang, Chen

AU - Dassama, Laura M.K.

AU - Zhang, Bo

AU - Guo, Yisong

AU - Rajakovich, Lauren J.

AU - Bollinger, Jr., Joseph M.

AU - Krebs, Carsten

AU - Van Der Donk, Wilfred A.

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N2 - Activation of O-H bonds by inorganic metal-oxo complexes has been documented, but no cognate enzymatic process is known. Our mechanistic analysis of 2-hydroxyethylphosphonate dioxygenase (HEPD), which cleaves the C1-C2 bond of its substrate to afford hydroxymethylphosphonate on the biosynthetic pathway to the commercial herbicide phosphinothricin, uncovered an example of such an O-H-bond-cleavage event. Stopped-flow UV-visible absorption and freeze-quench Mössbauer experiments identified a transient iron(IV)-oxo (ferryl) complex. Maximal accumulation of the intermediate required both the presence of deuterium in the substrate and, importantly, the use of 2H2O as solvent. The ferryl complex forms and decays rapidly enough to be on the catalytic pathway. To account for these unanticipated results, a new mechanism that involves activation of an O-H bond by the ferryl complex is proposed. This mechanism accommodates all available data on the HEPD reaction.

AB - Activation of O-H bonds by inorganic metal-oxo complexes has been documented, but no cognate enzymatic process is known. Our mechanistic analysis of 2-hydroxyethylphosphonate dioxygenase (HEPD), which cleaves the C1-C2 bond of its substrate to afford hydroxymethylphosphonate on the biosynthetic pathway to the commercial herbicide phosphinothricin, uncovered an example of such an O-H-bond-cleavage event. Stopped-flow UV-visible absorption and freeze-quench Mössbauer experiments identified a transient iron(IV)-oxo (ferryl) complex. Maximal accumulation of the intermediate required both the presence of deuterium in the substrate and, importantly, the use of 2H2O as solvent. The ferryl complex forms and decays rapidly enough to be on the catalytic pathway. To account for these unanticipated results, a new mechanism that involves activation of an O-H bond by the ferryl complex is proposed. This mechanism accommodates all available data on the HEPD reaction.

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