An enzyme with improved anti-atherosclerotic and detoxiftying activities.
The enzyme Paraoxonase 1 (PON1) resides on HDL in the blood. The levels of PON1 and its catalytic proficiency appear to have a major impact on susceptibility to atherosclerosis, cardiac and vascular diseases, cholesterol reducing drugs and various toxins and pollutants, such as organophosphates (pesticides and nerve gases). However, when trying to use the human PON1 one encounters several problems, including its insolublilty and the lack of recombinant PON variants that can be expressed and manipulated in bacteria. The current technology offers new, genetically-engineered PON1 variants that are expressed in a fully functional form, at multi-miligram quantities and unprecedented purity.
PON1 resides within the cholesterol-carrying particles HDL and exhibits a multitude of activities related to the metabolism of drugs, lipids and other molecules associated with atherosclerotic vascular and cardiac diseases. The outlined technology utilized directed evolution in the laboratory, which yielded a series of variants that are 50-200 fold more proficient than native PON1 in different physiologically relevant tasks