Enzymatic Oxidative Cascade for Oxofunctionalization of Fatty Acids in One-Pot.

ABSTRACT

The biocatalytic conversion of fatty acids to α-ketoacids was accomplished by the action of two enzymes combined in a simultaneous one-pot two-step cascade. In the first step, P450 monooxygenase from Sphingomonas paucimobilis used hydrogen peroxide in the so-called peroxygenase mode for the regio- and enantioselective formation of α-hydroxyacids. In the next step, these hydroxyacid intermediates were further oxidized to the corresponding α-ketoacids by an α-hydroxyacid oxidase from Aerococcus viridans at the expense of molecular oxygen, thereby regenerating hydrogen peroxide used in the first step. Overall, the cascade was designed to employ catalytic quantities of hydrogen peroxide and proceeded at room temperature in dilute aqueous H2O2 solutions (≤0.01%). This setup could be applied to the conversion of a range of fatty acids (C60 to C100) and was scaled up to allow the production of 2-oxooctanoic acid in 91% isolated yield.