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

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

Nature chemical biology (2007-01-16)
Danica P Galonić, Eric W Barr, Christopher T Walsh, J Martin Bollinger, Carsten Krebs
ABSTRACT

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 alpha-ketoglutarate (alphaKG, 1), chloride and oxygen. To investigate the ability of these enzymes to functionalize unactivated methyl groups, we characterized the chlorination of the gamma-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 alphaKG-dependent hydroxylases.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
D-2-Aminobutyric acid, 98%
Sigma-Aldrich
L-2-Aminobutyric acid, BioReagent, suitable for cell culture
Sigma-Aldrich
DL-2-Aminobutyric acid, ReagentPlus®, 99%
Sigma-Aldrich
L-2-Aminobutyric acid, ≥99% (titration)