Evolved stereoselective hydrolases for broad-spectrum G-type nerve agent detoxification.

A preferred strategy for preventing nerve agents intoxication is catalytic scavenging by enzymes that hydrolyze them before they reach their targets. Using directed evolution, we simultaneously enhanced the activity of a previously described serum paraoxonase 1 (PON1) variant for hydrolysis of the toxic S(P) isomers of the most threatening G-type nerve agents. The evolved variants show ≤340-fold increased rates and catalytic efficiencies of 0.

Directed evolution of hydrolases for prevention of G-type nerve agent intoxication.

Organophosphate nerve agents are extremely lethal compounds. Rapid in vivo organophosphate clearance requires bioscavenging enzymes with catalytic efficiencies of >10(7) (M(-1) min(-1)). Although serum paraoxonase (PON1) is a leading candidate for such a treatment, it hydrolyzes the toxic S(p) isomers of G-agents with very slow rates.

Organophosphate degrading microorganisms and enzymes as biocatalysts in environmental and personal decontamination applications.

One of the major challenges in dealing with chemical warfare agent (CWA) dispersal, whether in the battlefield or after a terror act, is decontamination and rehabilitation of any contaminated area. Organophosphates (OPs) are considered to be among the deadliest CWAs to date. Other OPs are used as pesticides in modern agriculture, and are considered environmentally hazardous.