New substances 15,000 times more effective in destroying chemical warfare agents

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.