First Artificial Enzyme Created by Evolution in a Test Tube

There’s a wobbly new biochemical structure in Dr. Burckhard Seelig’s lab at the University of Minnesota that may resemble what enzymes looked like billions of years ago, when life on earth began to evolve – long before they became ingredients for new and improved products, from detergents to foods and fuels. Dr. Seelig created the fledgling enzyme by using directed evolution in the laboratory. Working with colleague Dr. Gianluigi Veglia, graduate student Fa-An Chao, and other team members, Dr.Seelig subsequently determined the enzyme’s structure, which made its debut December 9 as an advance online publication in Nature Chemical Biology. Lab tests show that the enzyme (a type of RNA ligase, which connects two RNA molecules) functions as natural enzymes although its structure looks very different and it is flexible rather than rigid. Dr. Seelig speculates the new protein resembles primordial enzymes, before their current structures evolved. While a handful of groups worldwide are developing artificial enzymes, these groups use rational design to construct the proteins on computers. Instead, the Seelig lab employs directed evolution. "To my knowledge, our enzyme is the only entirely artificial enzyme created in a test tube by simply following the principles of natural selection and evolution," he says. Rational enzyme design relies on preconceived notions of what a new enzyme should look like and how it should function. In contrast, directed evolution involves producing a large quantity of candidate proteins and screening several generations to produce one with the desired function. With this approach, the outcome isn’t limited by current knowledge of enzyme structure. "Just as in nature, only the fittest survive after each successive generation," Dr. Seelig explains.
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