People have harnessed the power of enzymes for millennia, using biological processes to make things we enjoy, such as beer, bread, and pickles. Today we have a solid understanding of how those processes work and a better ability to control and direct them. Romas Kazlauskas, professor and director of graduate studies in Biochemistry, Molecular Biology, and Biophysics and a member of the BioTechnology Institute, is working on using those enzymatic processes to replace some of the chemical processes that are so ubiquitous in the modern world. Choosing biological pathways rather than chemical ones can provide many advantages, such as making reactions faster and more selective, and producing less waste. I sat down with Dr. Kazlauskas to discuss his work and find out more about what drives him.
When I was a kid, I had a chemistry set and was very impressed by the power of chemistry. I grew up in Cleveland and, when I was 13, the river caught fire. The Cuyahoga River ran through a heavily industrial area, and it caught on fire and burned for about an hour. So clearly there is a downside to chemistry as well. Enzymes are a way to use the power of chemistry without having the same kind of pollution issues.
Potentially. There are enzymes that could destroy pesticides and herbicides, so they could be used to detoxify things. We’re also working on enzymes that can make disinfectants, like for peracetic acid, so small amounts of those could also clean up bacteria and disinfect other pathogens.
A cool project that I worked on was with Tony Dean in Ecology, Evolution and Behavior, when we reconstructed ancestral enzymes. The idea was to find something that doesn’t exist in nature—enzymes that could work with unnatural things like a chemist would synthesize. When enzymes were first forming or evolving, they may have been less efficient, but also more general and able to catalyze different kinds of reactions. So we set out to reconstruct these ancestral enzymes with the hope that they would catalyze a broader range of reactions than the modern specialists. We found that some of these ancestral enzymes can indeed catalyze two seemingly incompatible reactions, whereas modern enzymes can only do one or the other.
Thinking about continuing evolution, if you take microbes and try to put selective pressure on them, they are often very creative, which means you don’t get what you think you’re going to get. You want a certain thing to happen, and they will find a way around the barrier you’ve put there (like a mutation), but often not in the way you hoped. People have developed methods to focus mutagenesis on one particular enzyme rather than letting the target come up with its own creative solutions. If you turn on mutagenesis in general, it’s a mess, but this lets us target one gene or pathway.
I teach a course on protein engineering, and it’s still hard to make predictions. That’s why people use evolution, especially when things are more complicated. I think in the next decade people are going to get better at predicting what they should change in order to make the enzyme more stable or make it more selective or expand it so it can accept an unusual substrate.
Hiking, canoeing, going into nature. In early March we’re going up to the North Shore to a cabin in Tettegouche State Park, so I’m looking forward to that. Going for walks with our dog to different places along the Mississippi is very nice. And we have really good bike paths in the Twin Cities. You can easily ride 10-15 miles in an hour, so that’s a nice way to spend some time enjoying nature.
I like the size—you can find people that are doing almost any possible research that you can think of. If you do a little searching, you can find a colleague that you can talk to and ask about that particular topic. I really like the Biotechnology Institute because of the opportunity to collaborate with people in different disciplines. I think this university is really good for that. The Institute brings us together with people from other departments and starts us thinking, which we just wouldn’t do if there wasn’t some way to get to know other faculty.