A mixture of three engineered phosphotriesterases enables rapid detoxification of the entire spectrum of known threat nerve agents. Issue 4 (15th October 2019)

• Record Type: Journal Article
• Authors: Despotović, Dragana; Aharon, Einav; Dubovetskyi, Artem; Leader, Haim; Ashani, Yacov; Tawfik, Dan S
• Editors: Fersht, Alan
• Is Part Of: Protein engineering, design & selection. Volume 32:Issue 4(2019)
• Page Start: 169
• Page End: 174
• Publication Date: 2019-10-15
• Subjects: enzyme cocktail -- organophosphate nerve agents -- phosphotriesterase -- protein engineering; Protein engineering -- Periodicals; 660.63
• DOI: 10.1093/protein/gzz039
• Languages: English
• ISSNs: 1741-0126

Abstract

Abstract: Nerve agents are organophosphates (OPs) 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.