Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase

Megan L. Matthews, Wei Chen Chang, Andrew P. Layne, Linde A. Miles, Carsten Krebs, Joseph M. Bollinger, Jr.

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Iron-dependent halogenases employ cis-halo-Fe(IV)-oxo (haloferryl) complexes to functionalize unactivated aliphatic carbon centers, a capability elusive to synthetic chemists. Halogenation requires (i) coordination of a halide anion (Cl - or Br -) to the enzyme's Fe(II) cofactor, (ii) coupled activation of O 2 and decarboxylation of α-ketoglutarate to generate the haloferryl intermediate, (iii) abstraction of hydrogen (H•) from the substrate by the ferryl and (iv) transfer of the cis halogen as Cl• or Br• to the substrate radical. This enzymatic solution to an unsolved chemical challenge is potentially generalizable to installation of other functional groups, provided that the corresponding anions can support the four requisite steps. We show here that the wild-type halogenase SyrB2 can indeed direct aliphatic nitration and azidation reactions by the same chemical logic. The discovery and enhancement by mutagenesis of these previously unknown reaction types suggest unrecognized or untapped versatility in ferryl-mediated enzymatic C-H bond activation.

Original languageEnglish (US)
Pages (from-to)209-215
Number of pages7
JournalNature Chemical Biology
Volume10
Issue number3
DOIs
StatePublished - Jan 1 2014

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Anions
Carbon
Iron
Decarboxylation
Halogens
Halogenation
Mutagenesis
Hydrogen
Enzymes
alpha-ketoglutaric acid

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

Cite this

Matthews, Megan L. ; Chang, Wei Chen ; Layne, Andrew P. ; Miles, Linde A. ; Krebs, Carsten ; Bollinger, Jr., Joseph M. / Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase. In: Nature Chemical Biology. 2014 ; Vol. 10, No. 3. pp. 209-215.
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Direct nitration and azidation of aliphatic carbons by an iron-dependent halogenase. / Matthews, Megan L.; Chang, Wei Chen; Layne, Andrew P.; Miles, Linde A.; Krebs, Carsten; Bollinger, Jr., Joseph M.

In: Nature Chemical Biology, Vol. 10, No. 3, 01.01.2014, p. 209-215.

Research output: Contribution to journalArticle

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