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Human-Directed Evolution in Petri Dish Creates Artificial Proto Enzyme

First Posted: Feb 01, 2013 03:44 PM EST

Human-directed evolution in a petri dish led to the creation of what is believed to resemble a primordial enzyme, one of the first elements of life billions of years ago which doesn't exist anymore today since proteins evolved to have a different form.

The wobbly new biochemical structure in Burckhard Seelig's lab at the University of Minnesota, a type of RNA ligase which connects two RNA molecules, works exactly as was desired by the scientist, but it is flexible instead of rigid, compared to its natural sibblings.

For decades, naturally occurring enzymes have been tweaked by industry to make industrial processes and products more effective. The ability to create enzymes from scratch using a natural process is synthetic biology at its best and likely opens the door to a vast array of new products that provide business opportunities and improve quality of life without harmful environmental effects.

evolved enzyme RNA ligase
(Photo : University of Minnesota)
3-D structure of the evolved enzyme (an RNA ligase), using 10 overlaid snapshots. In the top region, the overlays show the range of bending and folding flexibility in the amino acid chain that forms the molecule. The two gray balls are zinc ions.
Going forward, Seelig plans to create enzymes with useful applications while he continues to explore the underlying basic science of enzyme structure and function, aiming to learn more about the origin of enzymes and how proteins evolve.

"Enzymes have always fascinated me," he says. "It's rewarding to do work that has practical applications yet provides the opportunity to better understand how life on earth evolved."

While artificial enzymes are already developed by several groups worldwide , 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.

Fa-An Chao et al., Structure and dynamics of a primordial catalytic fold generated by in vitro evolution, Nature Chemical Biology, 2012, DOI: 10.1038/nchembio.1138

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