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 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 language | English (US) |
---|---|
Pages (from-to) | 113-116 |
Number of pages | 4 |
Journal | Nature Chemical Biology |
Volume | 3 |
Issue number | 2 |
DOIs | |
State | Published - Feb 2007 |
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology