Engineering Enzymes from Scratch
Researchers design catalysts using a novel computational technique
Source: “De Novo Computational Design of Retro-Aldol Enzymes”
David Baker et al.
Science 319: 1387-1391
Results: Scientists from the University of Washington designed enzymes that cause a synthetic chemical to break down 10,000 times as quickly as it would on its own; then they built the enzymes from scratch. No natural enzymes perform the same task.
Why it matters: Novel enzymes that catalyze chemical reactions not normally seen in nature could lead to new ways to make drugs and biofuels and to clean up environmental toxins. Because enzymes are so structurally complex, however, designing new ones has proved extremely difficult.
Methods: In a biochemical reaction, an enzyme acts on a substrate. Small pockets in the enzyme that bind only to particular substrates give the molecule both its catalytic effect and its specificity. Researchers used a combination of methods, including some that involved quantum chemistry, to design a pocket that they predicted would catalyze the desired reaction. Then they used a series of novel algorithms to model candidate enzymes incorporating the pocket. Finally, the researchers synthesized the proteins and tested their catalytic activity.
Next steps: The researchers want to make the new enzymes as efficient as naturally occurring enzymes, which can increase the rate of a reaction a quadrillion-fold. To do that, they are both improving the algorithms used to generate model proteins and modifying the newly designed enzymes through directed evolution–making a variety of small changes to the enzymes and seeing which ones boost efficiency.