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USING a process called structure-guided recombination a Caltech chemical engineer has taken the first step in concocting a more efficient and stable suite of cellulose-degrading enzymes.

Natural sugars are easily processed into biofuels such as ethanol and butanol but getting hold of the sugars in the first place is not so easy. Corn is a popular feedstock for ethanol production but is expensive because of competing food demands. An abundant cheaper alternative is the corn stover, comprising the inedible leaves, stalks and stripped cobs, but this waste is costly to process into sugars because it contains a significant portion of cellulose that is notoriously difficult to degrade requiring specific enzymes, or cellulases, for each processing step.

Until now, industrial efforts to process cellulose have made use of natural cellulases from plant-decaying filamentous fungi but these only operate in a narrow temperature range below 50°C. California Institute of Technology’s professor of chemical engineering Frances Arnold knew that the ideal enzymes operate between 70°C and 80°C because reactions run quicker at higher temperatures and cellulose expands becoming easier to breakdown.

With this in mind, he set about using a computer programme to ‘mate’ the sequences of three known fungal cellulases to make 6000 progeny sequences, each slightly different from each other and the parent sequence but all coding for proteins with a  structure necessary to degrade cellulose. Analysing a small subset of the resulting sequences, Arnold and gene-synthesis company DNA2.0 determined which would be stable at high temperatures and put them in yeast, which produced the new cellulases.

Previously, there were fewer than ten known fungal cellobiohydrolase II enzymes but Arnold and DNA2.0 managed to create 15 new highly-stable enzymes that work at 70°C to 75°C degrading more cellulose than the parent enzymes.

Arnold and DNA2.0 will now use the structure-guided recombination process to improve each of the half-dozen or so cellulases used for the industrial degradation of cellulose.

“We've demonstrated the process on one of the components,” says Arnold. “Now we have to create families of all of the other components, and then look for the ideal mixtures for each individual application.”