First artificial enzyme created by evolution in a test tube
February 1, 2013
There’s a wobbly new biochemical structure in 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.
Working with team members, he subsequently determined its structure.. 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.
Using directed evolution
While a handful of groups worldwide are developing artificial enzymes, they use rational design to construct the proteins on computers. Rational enzyme design relies on preconceived notions of what a new enzyme should look like and how it should function.
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.
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,” Seelig explains. The process continues until it produces an enzyme that efficiently catalyzes a desired biochemical reaction. In this case, the new enzyme joins two pieces of RNA together.
Natural enzymes, like all proteins, are made from alpha helices and beta strands. Seelig’s artificial enzyme lacks those structures. Instead, it forms around two metal ions and is not rigid.