Researchers unveil first artificial enzyme created by evolution in test tube

January 30, 2013, 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. Credit: University of Minnesota / Peggy Rinard
(—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 – long before they became ingredients for new and improved products, from detergents to foods and fuels.

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 . show that the enzyme (a type of RNA ligase, which connects two ) 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, and and Seelig is member of the BioTechnology Institute.

While a handful of groups worldwide are developing artificial enzymes, they use to construct the proteins on computers. Instead, the Seelig lab employs directed evolution. "To my knowledge, our enzyme is the only entirely 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," 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.

"It's kind of like giving typewriters to monkeys," he says. "One monkey and one typewriter won't produce anything clever. But if you have enough monkeys and typewriters, eventually one of them will write 'to be or not to be'." The lottery provides another analogy. "If you buy more tickets, you're more likely to win," Seelig says.

Like all proteins, the new RNA ligase enzyme is a chain of amino acids folded into a 3D structure, but the resemblance stops there. , 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. "Compared to enzymes we know from nature, the artificial enzyme has a rather unusual structure and dynamics," Seelig says.

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 opens the door to a vast array of new products that provide business opportunities and improve quality of life without harmful environmental effects.

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 evolved."

Explore further: Enzyme created in test tube displays new structure, function

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5 / 5 (12) Jan 30, 2013
A much better analogy would be that every time a monkey made a word or phrase, that word became available to all of the monkeys on their keyboards. Rather rapidly, the keyboards would be dominated by words and phrases.
1.2 / 5 (21) Jan 30, 2013
In this case, "directed evolution" = intelligent design, assuming that the researchers are intelligent, of course. So if this work demonstrates how life on Earth evolved, does that mean that Seelig feels that life on Earth arose via "directed evolution"?
5 / 5 (10) Jan 30, 2013
In this case, "directed evolution" = intelligent design, assuming that the researchers are intelligent, of course. So if this work demonstrates how life on Earth evolved, does that mean that Seelig feels that life on Earth arose via "directed evolution"?

No. Directed evolution here refers to the specific feature the scientist wants to target. In nature, the target is only reproduction. All means to achieve it are possible outcomes of natural selection. Thus the huge diversity of life. Scientists don't want "anything" to come out as it would require too much time and energy to let their experiments evolve blindly. So they must provide a specific criteria for selection, thus the "directed" term.
5 / 5 (3) Jan 30, 2013
I wonder how well this particular enzyme functions compared to natural enzymes that do the same task.
5 / 5 (1) Jan 30, 2013
@LariAnn: I think the previous technique "Rational enzyme design" would be the intelligent design pattern, not the new "directed evolution" pattern. Especially since rational and intelligent are synonyms :)
5 / 5 (7) Jan 30, 2013
In this case, "directed evolution" = intelligent design...

...and one logical extension is that invisible super-beings aren't required.
5 / 5 (2) Jan 30, 2013
Artificial selection to make proteins has been suggested and worked on for decades now. I remember years ago, they said, "we just made a five hundred percent increase in artificial evolution of proteins", and then nothing much came out of it; but, then, there was another improvement, and then like last December, a guy by the name of Baker I do believe made protein engineering even better; so much better, that some see or believe that the protein pathway to nanomanufacturing has come of age. Since then, I've seen examples before this; this is proof that the artificial evolution of proteins pathway to nanomanufacturing seems to be happening now.

Whydening Gyre
1.6 / 5 (7) Jan 31, 2013
The fact that it took nature a billion years to do this, using trillions upon trillions of combinations should be a pretty good indicator of the LACK of intelligent design and the increased importance of probability.
So, Either there is no God or she's a gambler...
Might be the one comment Einstein got wrong - or not...
not rated yet Feb 04, 2013
The term directed evolution threw me off for a bit. I thought they were referring to directed mutagenesis, the sort of thing John Cairns studies in E coli. Perhaps this is my ignorance talking, but wouldn't the term artificial selection be more apt?
not rated yet Feb 04, 2013
"Especially since rational and intelligent are synonyms"

Rational and intelligent are neither synonyms nor synonymous. It's quite possible, and in fact happens rather often, to be highly intelligent while being totally irrational [hence the saying "there's method to his/her madness]. And we're all familiar with rational but dim individuals, they make up the bulk of the head count in bureaucracies and back-offices everywhere and at all levels.

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