%0 Journal Article %A Dragana Despotovic %A Einav Aharon %A Artem Dubovetskyi %A Haim Leader %A Yacov Ashani %A Dan S. Tawfik %T A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents %D 2019 %R 10.1101/748749 %J bioRxiv %P 748749 %X 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.OPorganophosphatePTEphosphotriesteraseOPNAorganophosphate nerve agentOPHorganophosphate hydrolaseRVXRussian VX %U https://www.biorxiv.org/content/biorxiv/early/2019/08/28/748749.full.pdf