In an advance that could be used in masks to protect against nerve gas, scientists are reporting development of proteins that are up to 15,000 times more effective than their natural counterpart in destroying chemical warfare agents. Their report appears in ACS' journal Biochemistry.
Frank Raushel, David Barondeau and colleagues explain that a soil bacterium makes a protein called phosphotriesterase (PTE), which is an enzyme that detoxifies some pesticides and chemical warfare agents like sarin and tabun. PTE thus has potential uses in protecting soldiers and others. Natural PTE, however, works against only one of the two molecular forms of these chemical warfare agents, and it happens to be the less toxic form. The scientists thus set out to develop new versions of PTE that were more effective against the most toxic form.
To improve the enzyme's activity, Raushel and colleagues used an approach called "directed evolution." This technique imitates the way natural selection leads to improved forms of the biochemical substances in living things. In using directed evolution, the team made small random changes to the natural enzyme's chemical architecture and then tested resulting mutant enzymes for their ability to break down nerve agents. They isolated several mutants that fit the bill, including one that proved to be 15,000 times more effective than the natural enzyme.
The authors acknowledge funding from the National Institutes of Health.
- Ping-Chuan Tsai, Nicholas Fox, Andrew N. Bigley, Steven P. Harvey, David P. Barondeau, Frank M. Raushel. Enzymes for the Homeland Defense: Optimizing Phosphotriesterase for the Hydrolysis of Organophosphate Nerve Agents. Biochemistry, 2012; 120731143027000 DOI: 10.1021/bi300811t
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