TR10: Cellulolytic Enzymes

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By Alexandra M. Goho

Her latest strategy is a computational approach that can rapidly identify thousands of new protein sequences for screening. This approach generates many more sequence variants than other methods do, greatly increasing the chances of creating functional molecules with useful new properties.

Arnold is using the technique to build libraries containing thousands of new cellulase genes. She and her colleagues will then screen the cellulases to see how they act as part of a mixture of enzymes. "If you test them simply by themselves, you really don't know how they work as a group," she says.

To fulfill her ultimate goal of a superbug able to feed on cellulose and produce biofuels, Arnold is working with James Liao, a professor of chemical engineering at the University of California, Los Angeles. Liao recently engineered E. coli that can efficiently convert sugar into butanol, a higher-energy biofuel than ethanol. Arnold hopes to be able to incorporate her new enzymes into Liao's ­butanol-­producing microbes. Gevo, a startup cofounded by Arnold and based in Denver, CO, has licensed Liao's technology for use in the large-scale production of advanced biofuels, including butanol.

Overcoming cellulose's natural resistance to being broken down is "one of the most challenging protein-engineering problems around," says Arnold. Solving it will help determine whether low-­emission biofuels will ever be a viable substitute for fossil fuels.

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