The role of chloride in the mechanism of O(2) activation at the mononuclear nonheme Fe(II) center of the halogenase HctB.

Mononuclear nonheme Fe(II) (MNH) and α-ketoglutarate (α-KG) dependent halogenases activate O2 to perform oxidative halogenations of activated and nonactivated carbon centers. While the mechanism of halide incorporation into a substrate has been investigated, the mechanism by which halogenases prevent oxidations in the absence of chloride is still obscure. Here, we characterize the impact of chloride on the metal center coordination and reactivity of the fatty acyl-halogenase HctB.

More than just a halogenase: modification of fatty acyl moieties by a trifunctional metal enzyme.

The highly selective oxidative halogenations by non-heme iron and α-ketoglutarate-dependent enzymes are key reactions in the biosynthesis of lipopeptides, and often bestow valuable bioactivity to the metabolites. Here we present the first biochemical characterization of a putative fatty acyl halogenase, HctB, which is found in the hectochlorin biosynthetic pathway of Lyngbya majuscula. Its unprecedented three-domain structure, which includes an acyl carrier protein domain, allows self-contained conversion of the covalently tethered hexanoyl substrate.