Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA

Bo Zhang, Lauren J. Rajakovich, Devon Van Cura, Elizabeth J. Blaesi, Andrew J. Mitchell, Christina R. Tysoe, Xuejun Zhu, Bennett R. Streit, Zhe Rui, Wenjun Zhang, Amie K. Boal, Carsten Krebs, J. Martin Bollinger

Research output: Contribution to journalArticle

Abstract

The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published X-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated non-heme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a monoiron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is actually a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.

Original languageEnglish (US)
Pages (from-to)14510-14514
Number of pages5
JournalJournal of the American Chemical Society
Volume141
Issue number37
DOIs
StatePublished - Sep 18 2019

Fingerprint

Decarboxylation
Fatty acids
lauric acid
Fatty Acids
Iron
Substrates
Heme Oxygenase (Decyclizing)
Pseudomonas fluorescens
Catalytic Domain
Oxidoreductases
Crystal structure
Chemical activation
X-Rays
Ions
Proteins
X rays
Acids

All Science Journal Classification (ASJC) codes

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

Cite this

Zhang, Bo ; Rajakovich, Lauren J. ; Van Cura, Devon ; Blaesi, Elizabeth J. ; Mitchell, Andrew J. ; Tysoe, Christina R. ; Zhu, Xuejun ; Streit, Bennett R. ; Rui, Zhe ; Zhang, Wenjun ; Boal, Amie K. ; Krebs, Carsten ; Bollinger, J. Martin. / Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA. In: Journal of the American Chemical Society. 2019 ; Vol. 141, No. 37. pp. 14510-14514.
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abstract = "The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published X-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated non-heme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a monoiron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is actually a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.",
author = "Bo Zhang and Rajakovich, {Lauren J.} and {Van Cura}, Devon and Blaesi, {Elizabeth J.} and Mitchell, {Andrew J.} and Tysoe, {Christina R.} and Xuejun Zhu and Streit, {Bennett R.} and Zhe Rui and Wenjun Zhang and Boal, {Amie K.} and Carsten Krebs and Bollinger, {J. Martin}",
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Zhang, B, Rajakovich, LJ, Van Cura, D, Blaesi, EJ, Mitchell, AJ, Tysoe, CR, Zhu, X, Streit, BR, Rui, Z, Zhang, W, Boal, AK, Krebs, C & Bollinger, JM 2019, 'Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA', Journal of the American Chemical Society, vol. 141, no. 37, pp. 14510-14514. https://doi.org/10.1021/jacs.9b06093

Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA. / Zhang, Bo; Rajakovich, Lauren J.; Van Cura, Devon; Blaesi, Elizabeth J.; Mitchell, Andrew J.; Tysoe, Christina R.; Zhu, Xuejun; Streit, Bennett R.; Rui, Zhe; Zhang, Wenjun; Boal, Amie K.; Krebs, Carsten; Bollinger, J. Martin.

In: Journal of the American Chemical Society, Vol. 141, No. 37, 18.09.2019, p. 14510-14514.

Research output: Contribution to journalArticle

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T1 - Substrate-Triggered Formation of a Peroxo-Fe2(III/III) Intermediate during Fatty Acid Decarboxylation by UndA

AU - Zhang, Bo

AU - Rajakovich, Lauren J.

AU - Van Cura, Devon

AU - Blaesi, Elizabeth J.

AU - Mitchell, Andrew J.

AU - Tysoe, Christina R.

AU - Zhu, Xuejun

AU - Streit, Bennett R.

AU - Rui, Zhe

AU - Zhang, Wenjun

AU - Boal, Amie K.

AU - Krebs, Carsten

AU - Bollinger, J. Martin

PY - 2019/9/18

Y1 - 2019/9/18

N2 - The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published X-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated non-heme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a monoiron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is actually a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.

AB - The iron-dependent oxidase UndA cleaves one C3-H bond and the C1-C2 bond of dodecanoic acid to produce 1-undecene and CO2. A published X-ray crystal structure showed that UndA has a heme-oxygenase-like fold, thus associating it with a structural superfamily that includes known and postulated non-heme diiron proteins, but revealed only a single iron ion in the active site. Mechanisms proposed for initiation of decarboxylation by cleavage of the C3-H bond using a monoiron cofactor to activate O2 necessarily invoked unusual or potentially unfeasible steps. Here we present spectroscopic, crystallographic, and biochemical evidence that the cofactor of Pseudomonas fluorescens Pf-5 UndA is actually a diiron cluster and show that binding of the substrate triggers rapid addition of O2 to the Fe2(II/II) cofactor to produce a transient peroxo-Fe2(III/III) intermediate. The observations of a diiron cofactor and substrate-triggered formation of a peroxo-Fe2(III/III) intermediate suggest a small set of possible mechanisms for O2, C3-H and C1-C2 activation by UndA; these routes obviate the problematic steps of the earlier hypotheses that invoked a single iron.

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