Scientists develop proteins 15,000 times more effective at destroying chemical warfare agents

Scientists have developed proteins that are 15,000 times more effective than their natural counterpart in destroying chemical warfare agents.

The discovery, which could be used in masks to protect against nerve gas, was made by biochemistry scientists Frank Raushel and David Barondeau, along with colleagues. They explain that soil bacterium makes a protein called phosphotriesterase (PTE) which detoxifies some pesticides and chemical warfare agents like sarin and tabun.

In this light, PTE has several applications when it comes to protecting soldiers and others that operate in hazardous surroundings. Natural PTE, however, only works against the less toxic form of these chemical warfare agents, which is why the scientists set out to develop new versions of PTE that were more effective against the most toxic form.

To improve the activity of the enzyme Mr Raushel and colleagues used 'directed evolution', which imitates the way natural selection leads to improved forms of the biochemical substances in living things. Using the technique, the researchers made small random changes to the enzyme's chemical architecture, and tested the mutant enzymes for their ability to break down nerve agents.

Their results uncovered several mutants that could perform this task, one of which proved to be 15,000 times more effective than the natural enzyme. This could lead to more effective agents being developed for gas masks used in warfare.

The report noted: "Characterization of these mutants with the authentic G-type nerve agents has confirmed the expected improvements in catalytic activity against the most toxic enantiomers of GB, GD, and GF."

Additionally, the results support a combinatorial strategy of rational design and directed evolution as a powerful tool for the discovery of more efficient enzymes for the detoxification of organophosphate nerve agents.

The report, entitled 'Enzymes for the Homeland Defense: Optimizing Phosphotriesterase for the Hydrolysis of Organophosphate Nerve Agents', has been published in American Chemical Society's journal Biochemistry.

Posted by Neil Clark