CSU, Swiss scientists’ work published in Science magazine

It took about nine months for Todd Hyster to discover a scientific breakthrough, and by October 2012 to have it published in Science magazine.

And to think he almost became an orthodontist.

“I knew I liked science and math, I didn’t know I wanted to do organic chemistry. I actually thought I wanted to be a doctor or an orthodontist,” Hyster said. “I found in my chemistry and molecular biology class that I actually enjoy thinking about small things more than thinking about big macroscopic systems, and while I was taking my cell and chemical biology class I was also taking my first organic chemistry class, and that’s when I started to get the feeling than chemistry would be a better fit.”

Hyster, a fifth-year graduate student, collaborated with CSU chemistry professor Tomislav Rovis and scientists at the University of Basel in Switzerland to create a new enzyme that allows scientists to transform other molecules in more selective ways at a faster rate than previously possible.

Enzymes help rearrange molecules in very specific ways to change their function. In the human body, enzymes break down food and rebuild the molecules into something the body can use for energy. The combination of an enzyme and a metal is called a metalloenzyme.

Although metalloenzymes occur naturally, Hyster and Rovis’ experiment paired a bacterial enzyme and a metal to create an “unnatural enzyme” not found in nature. This artificial metalloenzyme helps solve problems that do not work with just a metal or just an enzyme, according to Rovis.

In the pharmaceutical industry, it takes chemists anywhere from weeks to months to create a single candidate for a drug. Decreasing the time it takes to make a compound allows testing to begin sooner.

“If you shorten the discovery time, then in theory you can make a lot more candidates and in theory you have a better chance (of success),” Rovis said. “You keep swinging at a pitch, and the more pitches you swing at the more chances you have for a home run.”

The collaboration that led to the success happened by accident.

While on sabbatical, Rovis met Thomas Ward, a scientist at the University of Basel, who had developed technology for artificial metalloenzyme synthesis. Rovis put Ward in touch with Hyster, and Hyster ended up going to Basel for three months to work on the project with Ward and Livia Knörr. There was no guarantee of success, according to Rovis.

“I thought there was large potential for it, but it could have died,” Rovis said. “You plant a seed, and it could die, or it could sprout into this big tree and without the right person on it, it would have died, and I think Todd was the right person. It’s beginning to flourish, and it will continue to do that.”

Ward praised Hyster for his motivation and creativity, calling him “the best graduate student I have ever seen” and an adviser’s dream Ph.D candidate.

Rovis provided direction for the project, but he credits about 90 percent of the work to Hyster.

“Todd is capable,” Rovis said. “My role sometimes is just cheerleader.”

However, Hyster said that Rovis’ guidance over the years helped him better approach problems and become a better scientist.

“If the training has gone well, by the time you get to your fourth or fifth year you should be able to make these (intellectual) leaps on your own, and your boss should be able to sit back and admire the fact that his approach worked,” Hyster said.

Hyster began work in organic chemistry volunteering in the lab of his undergraduate adviser at the University of Minnesota. He said he enjoys the puzzle-like complexity of the projects he works on, and that he wants to become a professor like Rovis.

The project was published Oct. 26 in Science magazine, a “tremendous honor” because of the few organic chemistry papers that Science publishes, according to Hyster.

A publication in Science is “every scientist’s dream,” according to Ward, because it is a tangible sign of the importance and originality of a project.

The most exciting part of the discovery process for Rovis is the initial success of a project, and then finishing it and sending off to someone who recognizes its impact. Having Science be that someone is “pretty high up on the list,” Rovis said.

Because of Hyster’s project, CSU now has a small facility and is able to do more metalloenzyme development. There is a lot of interest in artificial metalloenzymes, and Rovis said he hopes other scientists continue the work Hyster started.

“It really is a small step,” Rovis said. “It is a very significant step, but it’s a small step. It’s an awful lot left to do, and while we’ve opened up one fairly narrow area, in theory you should be able to open up in this direction, that direction, and then it becomes a field. Now it’s, in essence, a blade of grass; we want it to become a whole field.”