PT  - JOURNAL ARTICLE
AU  - Despotovic, Dragana
AU  - Aharon, Einav
AU  - Dubovetskyi, Artem
AU  - Leader, Haim
AU  - Ashani, Yacov
AU  - Tawfik, Dan S.
TI  - A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents
AID  - 10.1101/748749
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 748749
4099  - http://biorxiv.org/content/early/2019/08/28/748749.short
4100  - http://biorxiv.org/content/early/2019/08/28/748749.full
AB  - 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