An engineered enzyme that can protect mice against a close analog of the nerve agent sarin is described online this week in Nature Chemical Biology. This study offers new strategies for protein engineering and potentially new practical measures in the fight against bioterrorism.
Serum paraoxonase has previously been identified as an enzyme that could be used to break apart sarin. According to current estimates, the speed with which the natural enzyme can perform this reaction is not fast enough to protect someone exposed to the toxin. Engineered enzymes, or versions of the protein that have been modified to improve the enzyme’s function, offered more promise but still lacked sufficient power to function in the real world.
Now Dan Tawfik and colleagues have created ways to test the enzyme that more accurately reflect how the protein would need to function in humans. This allowed the authors to screen through a huge number of new enzymes, and resulted in the identification of an enzyme with only 6 mutations that could protect mice against a sarin analog in a preventative assay.