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Nat Chem Biol. 2014 Mar;10(3):209-15. doi: 10.1038/nchembio.1438. Epub 2014 Jan 26.

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

Author information

  • 11] Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA. [2].
  • 2Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA.
  • 31] Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA. [2].
  • 41] Department of Chemistry, The Pennsylvania State University, University Park, Pennsylvania, USA. [2] Department of Biochemistry and Molecular Biology, The Pennsylvania State University, University Park, Pennsylvania, USA.

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 O2 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.

PMID:
24463698
PMCID:
PMC4076429
DOI:
10.1038/nchembio.1438
[PubMed - indexed for MEDLINE]
Free PMC Article
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