Rational design of paraoxonase 1 (PON1) for the efficient hydrolysis of organophosphates

Abstract

A rational design of paraoxonase 1 based on molecular docking discovered H115W/T332S and I74F/H115W/T332S mutants exhibited a 40-fold increase in catalytic efficiency (k_cat/K_m) toward the hydrolysis of two toxic and popular organophosphates (diethyl-paraoxon and dimethyl-paraoxon). Moreover, the conversion of the paraoxons (741.3–825.6 mg L⁻¹) by the evolved mutants was 42–60-fold faster than that by the wild type.