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The algorithm was able to analyse the evolutionary history of the enzyme and helped researchers create an improved version with the same structure.
A group of researchers – including Trinity College Dublin scientists – have created an algorithm to improve the design of enzymes, which could benefit various industries and peoples’ health.
Enzymes are proteins that speed up various chemical reactions and are essential for various functions of the body. There are a wide variety of enzymes, with some being vital for digestion, liver function and other bodily purposes. They also serve an important role for industries such as in the production of food and drugs.
These proteins have evolved over billions of years and have a wide variety in terms of their structure, being composed of hundreds of different amino acids to make up their 3D shape. Changing this structure and the type of amino acids could lead to ways of improving their effectiveness, which would benefit various sectors.
The researchers said changing the structure of an enzyme is simple and cost-effective. But doing it properly is complicated, as making random, tiny changes can alter the function of an enzyme – it can also reduce its function or make it entirely ineffective.
To address this issue, a research team developed an algorithm that takes into account the evolutionary history of an enzyme. The algorithm was designed by researchers at Broad Institute and Harvard Medical School.
Boosting an enzyme
To test this algorithm, the researchers looked to engineer an enzyme called beta-lactamase – a class of enzymes produced by bacteria. They then used this algorithm to assess how it can be altered to improve performance.
Dr Amir Khan, an associate professor at Trinity and co-author of the study, said the algorithm includes a “scoring function” that exploits thousands of sequences of beta-lactamase from “many diverse organisms”.
“Instead of a few random changes, up to 84 mutations over a sequence of 280 were generated to enhance functional performance,” Khan said. “And strikingly, the newly designed enzymes had both improved activity and stability at higher temperatures.”
Eve Napier, a second-year PhD candidate at Trinity, analysed the experimental structure of the team’s newly designed beta-lactamase, using a method called x-ray crystallography. This analysis suggested that the designed enzyme had an identical structure to the original enzyme, despite having changes to 30pc of its amino acids.
“Overall, these studies reveal that proteins can be engineered for improved activity by dramatic ‘jumps’ into new sequence space,” Napier said.
“The work has wide-ranging applications in industry, in processes that require enzymes for food production, plastic-degrading enzymes, and those relevant to human health and disease, so we are quite excited for the future possibilities.”
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