Engineering Enzymes: Steps in the Right Direction
Posted by Jenna Capyk on December 6, 2011
Enzymes: you’ve heard me rave about their incredible abilities before and you’ll hear it again. These specially-abled proteins can perform in microseconds all kinds of nifty chemistry that would otherwise take centuries or even millennia. In order to accomplish their specific chemical tasks, each enzyme has been honed by thousands of years of evolution to have the specificity and chemical capacity necessary to keep all biological systems alive and ticking.
Of course, scientists, with their big egos (kidding) aren’t going to be out-done by natural selection. Oh no, they have to go ahead and make their OWN enzymes. Really, a group of scientists form the University of Michigan reported this week in Nature Chemistry that they’ve managed to create an enzyme “de novo” (read: from scratch) that is able to perform the same chemical reaction as one of our own enzymes.
What enzyme did these scientists create? They created a whole new enzyme, but its reactivity is based on human carbonic anhydrase II. This enzyme takes carbon dioxide and water and spits out carbonate and protons. Like all enzymes, the natural carbonic anhydrase has a specific shape that contains a small location called the active site and this is where the chemistry happens. The scientists in Michigan came up with an entirely new shape, totally new scaffold, and stuck in something that looks a bit like the carbonic anhydrase active site. The result: it works. Well, it is able to perform the same carbon dioxide transformation as well as another reaction that carbonic anhydrase catalyzes. How well does this frankinenzyme do what it was literally designed to do? About 550 times less well than the natural enzyme, but to be fair, natural evolution has had a lot longer to work on it.
Now, you might argue that this type of research is completely unnecessary: wasting money to reinvent the wheel. Why would anyone ever spend tons of time and resources on designing an enzyme, from scratch no less, that is far less efficient than an enzyme that already exists in nature? If you made this argument, however, I would argue that your argument is wrong. This work is an incredibly interesting and important step forward in our understanding of how enzymes work. You can tinker with an engine all you want, but you won’t really understand one (or so I’m told) until you put it together from the individual pieces. The same is true for enzymes. By starting from scratch and designing this protein from the bottom up, these scientists are testing our understanding of the fundamental principles governing enzyme function. The fact that this totally synthetic protein is able to perform the exact chemistry it was designed to catalyze demonstrates that we have a decent grasp on the basics of how enzymes work, and that we can apply these concepts to create proteins that perform specific reactions.
As mentioned above, the specific reaction that this novel enzyme performs is already catalyzed by a natural enzyme. In fact, it’s catalyzed really quickly by a natural enzyme. So why did this group decide to target a reaction that we already have in our biological tool-belt? The answer is that they needed something to compare it against. The natural enzyme is kind of a benchmark that we can work toward. Using this standard enables scientists to create what can then be deemed an “efficient” enzyme. Without having a natural enzyme to compare it to, there’s no way to tell how fast the chemistry really has to be to be considered “good”. Having this benchmark allows these scientists to evaluate their progress with a realistic goal in mind.
So where does this type of research lead? This progress represents a really interesting development because it is moving toward creating brand-spanking-new enzymes to perform chemistry that is not already covered by naturally evolved enzymes: think breaking down Styrofoam, or any number of other human-created chemicals nature has a tough time getting rid of. Scientists have been working on the same problem by altering existing enzymes, but creating them from scratch might prove to be a strategy allowing for a broader range of novel chemical reactions.
Some people might call this type of research playing God, I like to think of it as playing Evolution, or at least learning from it.
Want to know more? Check out my blog post at And That’s Science! While you’re there you can read some of the other posts about what enzymes are, what they do, and how.