Seelig created the fledgling enzyme by using directed evolution in the laboratory. Working with colleague Gianluigi Veglia, graduate student Fa-An Chao, and other team members, he subsequently determined its 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 like natural enzymes although its structure looks very different and it is flexible rather than rigid. Seelig speculates the new protein resembles primordial enzymes, before their current structures evolved.
Seelig and Veglia are professors in the College of Biological Sciences, where Fa-An Chao is a graduate student. Both faculty members have appointments in the Department of Biochemistry, Molecular Biology and Biophysics and Seelig is member of the BioTechnology Institute.
While a handful of groups worldwide are developing artificial enzymes, they 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.