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bioRxiv · 10.1101/748749

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

Despotovic, D.·Aharon, E.·Dubovetskyi, A.·Leader, H.·Ashani, Y.·Tawfik, D. S.
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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.

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Despotovic, D., Aharon, E., Dubovetskyi, A., Leader, H., Ashani, Y., Tawfik, D. S.. 2019-08-28. A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents. https://doi.org/10.1101/748749

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