First artificial enzyme created by evolution in a test tube
February 1, 2013
3D 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)
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.
Seelig created the fledgling enzyme by using directed evolution in the laboratory.
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.
Comments (9)
by Andre
Similar to Dzaster, my knowledge on the subject borders on total ignorance.
What would be interesting is the basis on which the assumption what enzymes looked like “billions” of years ago is based.
As far as evolution is concerned, is it not a “non-directional, random process? Thus to use “directed” evolution, a primary assumption of evolution is left out of the equation and intelligence introduced.
by Ralph Dratman
This strikes me as a major achievement, one which could become important in studies of the beginnings of life. I would have liked to see more about the directed evolution techniques used to create this enzyme.
by de Broglie
I am very surprised at this development. About a month ago, I argued with my friend that this was unlikely in the near future. Proteins are so complicated I thought making an effecitve active site would be too difficult. Enzyme design is something that has a clear cut relationship to increasing computer processing power. The developments by the end of the decade will be amazing.
by Mjr_Dzaster
Too technical for this High School Drop Out…although I dropped out because I had a horrible time in high school, middle school and elementary school. Turns out decades later, when getting my eighteen month old son’s (who is now twenty years old) hearing tested by one of the top ENT specialists in Los Angeles because of continuing ear infections (my wife and I were new parents and didn’t know not to leave a bottle in our baby’s mouth while he sleeps…very bad for the Eustachian tubes, thus the ear canal).
Anyway, this doctor had me sit in this sound proof booth holding my son and giving me instructions for the hearing test since my son was only an infant at the time. Turns out that I was misunderstanding his instructions and reacting backwards to what he wanted me to do with my son. So he suggested that he’d like to give ME a hearing test. I told him that I didn’t have health coverage (couldn’t afford it) and he said that he wouldn’t charge me for the test. So I took a test. Afterwards, he asked me if I had had a hard time in school when I was growing up. I told him I had and that I had ditched school more than I was ever IN school and eventually I had to drop out (which was the best thing I ever could have done for myself).
This doctor asked me if I had ever heard of Auditory Dyslexia. I said that I had not. He told me that this was a relatively new discovery, although the “disorder?” has been around for decades if not for millennia…only it had never been diagnosed correctly or properly. Which is interesting because I was told that I was lazy, stupid, lacked interest and so on not just by my very frustrated parents, but also by teachers who just weren’t cognizant enough to dig a little deeper into kids who have comprehension or brain wiring problems. This was a HUGE discovery for me and helped me with life in general, but also helped me with my work and understanding the world around me.
So although I am not well educated in the academic sense, when I dropped out of high school, the principal of the local elementary school where I received my GED or high school equivalency told me that my test scores placed me at the sophomore university level. I had dropped out of high school in the third month of my freshman year. I also didn’t study for the tests. I decided to just go in and take them to get them over with because I hated the general public school format and really hated being tested THAT much.
I think the reason why you don’t see very many comments on this site or on specific articles has more to do with the fact that intelligent people who are reading these articles don’t want to spend their brain power on something as trivial as making comments unless they can contribute something of significance to the comments section. It’s time saving not to. In my case, well, I just HAD to comment, and that’s where time/energy/brain energy…i.e. thought energy can be tossed about a bit or in my case, used or wasted because I may not really have contributed anything of significance to this particular article. But you get my drift.
by asiwel
I appreciate your comments and the time it takes to write them. (We are fortunate at this site that most comments are interesting and well-intended.) In my experience, your story, unfortunately, is often the case … but, even more unfortunately … not “more often than not.” Learning disabilities – limited vision, hearing and reading issues, etc. – are real afflictions that some can overcome/compensate for while others struggle more futilely. But the drop-out problem is much more than this … and more than simply another of our (actually fairly good, at least potentially) educational system’s shortcomings. Dropping out is not the end of “hope” … relatively few drop out for lack of talent or innate ability to succeed and may always drop back in in various ways. But the vicissitudes of life and growth and responsibilities stack the probabilities against that.
by WLGJR
BTW, it is sad to see that some articles in KurzweilAI are never commented, such as some on bioinformatics (not all though). Too technical (for commentators), I guess?
by trakk
Throw in words like ‘quantum’ or ‘singularity’ and they will jump in :-)
by WLGJR
Keep evolving. I wonder whether evolving them in a supercomputer is possible. I mean, without the messiness of real molecules.
by Anthony
Simulated evolution is certainly faster than actual evolution!