Researchers have developed a new approach to “rationally engineering” enzymes in order to enhance their performance. They have created an algorithm that considers an enzyme’s evolutionary history to identify where mutations could be made to achieve functional improvements. This work could have significant and far-reaching effects on a variety of industries, including food production and human health.
Researchers have identified specific regions in the evolutionary history of enzymes where mutations could be made to potentially improve their functionality.
This study, published today in the prestigious journal Nature Communications, could have widespread impacts in various industries, such as food production and human health.
Enzymes play a crucial role in life and are essential for developing new drugs and solutions to societal issues. Through billions of years of evolution, enzymes have changed their 3D structure due to alterations in the amino acid sequence. Each enzyme is like a string of beads, with each bead representing a sequence of amino acids.Finding ways to enhance the performance of enzymes would be extremely advantageous to various industries, including pharmaceuticals, agriculture, and biofuels. Enzymes play a crucial role in many biological processes, and enhancing their activity could lead to significant advancements in medicine, food production, and renewable energy. The sequence diversity of amino acids allows for the potential improvement of enzyme functionality, which could have far-reaching implications for various scientific and industrial fields.It is now simple and cost-effective to make changes to the amino acid sequences in order to improve performance in various industrial applications using modern molecular biology tools. However, making just a few changes to the sequence can significantly reduce the activity of the enzyme. Instead of randomly introducing mutations, scientists have developed a new approach to engineering the enzyme “beta-lactamase” using an algorithm that considers its evolutionary history. This promising strategy was developed by researchers at the Broad Institute and Harvard Medical School.
“This new algorithm is centered around a scoring function that takes advantage of numerous sequences of beta-lactamase from a wide range of organisms. Instead of making a few random changes, we generated up to 84 mutations over a sequence of 280 in order to improve functional performance,” explained Dr. Amir Khan, Associate Professor in Trinity College Dublin’s School of Biochemistry and Immunology, and one of the co-authors of the study.
“Remarkably, the newly designed enzymes displayed both enhanced activity and stability at higher temperatures.”
Eve Napier, a second-year PhD student at Trinity College, The researchers in Dublin used X-ray crystallography to determine the 3D structure of a newly designed beta-lactamase. The 3D map showed that despite altering 30% of the amino acids, the enzyme had the same structure as the wild-type beta-lactamase. It also demonstrated how coordinated changes in amino acids, made at the same time, can effectively stabilize the 3D structure, unlike individual changes which typically weaken the enzyme structure.
Eve Napier commented, “these studies show that proteins can be modified for better activity by making significant changes in the sequence space.”The potential impact of this research is vast, with applications in various industries such as food production, plastic degradation, and human health. We are eager to see where this work will lead in the future.
