Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3

Danica P. Galonić, Eric W. Barr, Christopher T. Walsh, J. Martin Bollinger, Carsten Krebs

Research output: Contribution to journalArticlepeer-review

278 Scopus citations


Enzymatic incorporation of a halogen atom is a common feature in the biosyntheses of more than 4,500 natural products. Halogenation of unactivated carbon centers in the biosyntheses of several compounds of nonribosomal peptide origin is carried out by a class of mononuclear nonheme iron enzymes that require α-ketoglutarate (αKG, 1), chloride and oxygen. To investigate the ability of these enzymes to functionalize unactivated methyl groups, we characterized the chlorination of the γ-methyl substituent of L-2-aminobutyric acid (L-Aba, 2) attached to the carrier protein CytC2 by iron halogenase (CytC3) from soil Streptomyces sp. We identified an intermediate state comprising two high-spin Fe(IV) complexes in rapid equilibrium. At least one of the Fe(IV) complexes abstracts hydrogen from the substrate. The demonstration that chlorination proceeds through an Fe(IV) intermediate that cleaves a C-H bond reveals the mechanistic similarity of aliphatic halogenases to the iron- and αKG-dependent hydroxylases.

Original languageEnglish (US)
Pages (from-to)113-116
Number of pages4
JournalNature Chemical Biology
Issue number2
StatePublished - Feb 2007

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology


Dive into the research topics of 'Two interconverting Fe(IV) intermediates in aliphatic chlorination by the halogenase CytC3'. Together they form a unique fingerprint.

Cite this