A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents

Abstract Nerve agents are organophosphates that potently inhibit acetylcholinesterase and their enzymatic detoxification has been a long-standing goal. Nerve agents vary widely in size, charge, hydrophobicity, and the cleavable ester bond. A single enzyme is therefore unlikely to efficiently hydrolyze all agents. Here, we describe a mixture of three previously developed variants of the bacterial phosphotriesterase ( Bd -PTE) that are highly stable and nearly sequence identical. This mixture enables effective detoxification of a broad spectrum of known threat agents – GA (tabun), GB (sarin), GD (soman), GF (cyclosarin), VX, and Russian-VX. The potential for dimer dissociation and exchange that could inactivate Bd -PTE has minimal impact, and the three enzyme variants are as active in a mixture as they are individually. To our knowledge, this engineered enzyme ‘cocktail’ comprises the first solution for enzymatic detoxification of the entire range of threat nerve agents.