Chemists Create Enzyme Mimic

Scientists have created a molecule that mimics the look and behavior of a natural enzyme, a workhorse protein that speeds up chemical reactions in living things. The achievement, described in tomorrow's issue of Science, may point the way to other enzyme mimics that could reduce the complexity and cost of many industrial reactions as well as lower their output of unwanted, polluting byproducts.

Researchers have been trying to mimic enzymes for decades. But their earlier models have had serious limitations: Even when they catalyze the same chemical reactions as the real enzymes, they rarely do so in the same way. And those that do faithfully duplicate an enzyme's function rarely resemble their mentor. Because nature has already figured out how to run complex reactions under environmentally friendly conditions, says Dan Stack of Stanford University, a molecule that looks and acts like the real thing should be more effective.

Stack's team decided to try to imitate an enzyme called galactose oxidase, which converts alcohols to aldehydes. The enzyme depends on a single copper atom at the core, which when properly positioned efficiently snatches electrons and gives them up to other atoms. Galactose oxidase achieves this configuration by forcing the copper atom to bind to five compounds--four amino acids and one water molecule--in a pyramid-shaped arrangement that keeps it a bit unsatisfied, looking for more action. Alcohols then kick out the water molecule, take its spot, and with a little bit of electron- and proton-swapping are converted to aldehydes.

To create the same reactive geometry in their model catalyst, Stack and his graduate student Yadong Wang designed a set of organic arms--one called a phenol, the other binaphthol--that would bind to the copper atom and mimic the role of galactose oxidase's key amino acids. The result is a compound that binds alcohols and then goes to work on them, much like the enzyme. Although the mimic works more slowly than the natural enzyme--perhaps because the alcohol molecule is more free to move around--Stack and Wang found that it duplicates the enzyme's reaction steps.

It "is quite an impressive piece of work," says Harvard University inorganic chemist Richard Holm. Holm and others suggest that structural studies of other enzymes should help modelers soon create other enzyme mimics. Nitrogenase, which takes nitrogen in the air and converts it to a biologically useful form by tacking on hydrogens, is among the modelers' most hotly pursued prizes. Concludes Stack: "The time is right for rapid progress in this area."