In Motion

Researchers investigate enzyme movement to improve ethanol production
By Kris Bevill | December 12, 2011

Scientists at the U.S. DOE’s Oak Ridge National Laboratory are combining fundamental knowledge of enzymes and new discoveries regarding their movement to potentially improve the ability to produce cellulosic ethanol and perhaps cure some of the world’s most notorious diseases.

“The importance of the structure of enzymes has been known for more than 100 years, but only recently have we started to understand that the internal motions may be the missing piece of the puzzle to understand how the enzymes work,” says Pratul Agarwal, ORNL staff scientist.

Using ORNL’s supercomputer, known as Jaguar, Agarwal and postdoctoral researcher Arvind Ramanthan investigated 12 enzymes at an atomistic scale and found that all enzymes have similar motions. “If something is important for function, then it will be present in the protein performing the same function across different species,” Agarwal says. “For example, regardless of which company makes a car, they all have wheels and brakes.”

Jaguar allowed Agarwal and Ramanthan to complete their investigation of enzymes in about one month, compared to the several years it would have taken otherwise. Their findings also showed that enzymes possess so-called knobs, which Agarwal says can be tweaked to improve the enzyme’s performance. “When we investigate the motions, we discover knobs on the enzymes which can be tuned to increase the efficiency,” he says. “Understanding the dynamics of the enzymes gives us control of the catalytic efficiency of the enzyme.”

Researchers will continue to identify various pathways, Agarwal says. Additionally, he and Ramanthan are involved in preparing a spin-off company that will build on their discovery, eventually allowing the technology to become commercially available. In late November, Agarwal said discussions were under way with ORNL’s technology transfer division to determine whether the company will be privately held. He anticipates that the company will be launched by May. The enzyme work conducted by Agarwal and Ramanthan could be useful not just for biofuels, but perhaps even more importantly for creating medicines that can cure diseases such as AIDS, he says. Agarwal previously identified a network of protein vibrations in the enzyme Cyclphilin A, which is involved in many biological reactions, including AIDS-causing HIV-1.

The results of Agarwal and Ramanthan’s research have been published in a paper titled “Evolutionary conserved linkage between enzyme fold, flexibility and catalysis” in PLoS Biology, a peer-reviewed scientific journal. Funding for their research was provided by ORNL’s Laboratory Directed Research and Development program. ORNL is managed by UT-Battelle for the DOE’s Office of Science.—Kris Bevill