Researchers have achieved a groundbreaking feat by successfully using extensive computer calculations to predict how to modify the optimal temperature of an enzyme. Their study, a collaboration between Uppsala University and the University of Tromsø, was published in the esteemed journal Science Advances.
The researchers focused on a cold-adapted enzyme derived from an Antarctic bacterium. Such enzymes are commonly found in bacteria and fish inhabiting frigid waters. Through evolution, these enzymes have developed the ability to function even in extremely low temperatures that would render other enzymes inactive. In comparison to enzymes from warm-blooded organisms and those thriving in higher temperatures, cold-adapted enzymes consistently exhibit lower optimum temperatures and melting points.
The team set out to investigate whether computer simulations of the catalyzed chemical reaction could predict a limited number of mutations that would raise the optimum temperature of the Antarctic enzyme. The calculations revealed that incorporating 16 mutations from the corresponding pig enzyme into the bacterial variant could achieve this desired outcome.
Subsequently, the researchers synthesized the hybrid enzyme and assessed its catalytic activity across different temperatures. Remarkably, the new variant exhibited a 6°C increase in its optimum temperature compared to the original version. Furthermore, at 50°C, it outperformed both the Antarctic and pig enzymes in terms of speed. To validate the structural changes predicted by the computer calculations, the team employed X-ray crystallography to determine the three-dimensional structure of the hybrid enzyme, confirming that the necessary alterations had indeed occurred.
In recent years, computer-based enzyme design has emerged as a prominent and highly pursued field of research. The objective is to create enzymes with novel properties, employing computer calculations instead of resource-intensive experimental methods.
“For instance, this could involve developing enzymes that catalyze chemical reactions absent in nature or modifying their properties to enhance their ability to withstand heat, cold, high pressure, increased salinity, and other challenging conditions. Consequently, this area has attracted significant biotechnological interest,” explains Johan Åqvist, Professor of Theoretical Chemistry at Uppsala University.
Source: Uppsala University