α-Oxidative decarboxylation of fatty acids catalysed by cytochrome P450 peroxygenases yielding shorter-alkyl-chain fatty acids

Abstract

Cytochrome P450 peroxygenases belonging to the CYP152 family catalyse the oxidation of fatty acids using H₂O₂. CYP152N1 isolated from Exiguobacterium sp. AT1b exclusively catalyses the α-selective hydroxylation of myristic acid at physiological H₂O₂ concentration. However, a series of shorter-alkyl-chain fatty acids such as tridecanoic acid were produced from myristic acid by increasing the concentration of H₂O₂ (1–10 mM). The yield of tridecanoic acid from myristic acid reached 17%. An ¹⁸O-labeled oxidant study suggested that CYP152N1 catalysed the overoxidation of α-hydroxymyristic acid to form α-ketomyristic acid, which in turn was spontaneously decomposed by H₂O₂ to yield tridecanoic acid. Crystal structure analysis of CYP152N1 revealed its high similarity to other CYP152 family enzymes, such as CYP152A1 and CYP152B1. MD simulations of α-hydroxymyristic acid accommodated in CYP152N1 proposed a possible pre-oxidation conformation of α-hydroxymyristic acid for the decarboxylation reaction.