This article has been reviewed according to Science X's editorial process and policies. Editors have highlighted the following attributes while ensuring the content's credibility: A new approach that changes just one atom in plastic-degrading enzymes could help make them more efficient while maintaining their stability, according to new research from The Australian National University published in Angewandte Chemie International Edition. Researchers have shown that making precise, single-atom changes to highly engineered enzymes can improve their ability to break down polyethylene terephthalate (PET)—one of the world's most widely used plastics—without compromising their stability.
Elwy Abdelkader, from the Research School of Chemistry, said the approach could help overcome a major challenge in enzyme engineering. "Enzymes can be engineered over and over again to improve their performance, but eventually you reach a point where making them more active can also make them less stable, and vice versa," Abdelkader said. "What we have shown is that you can go beyond this limit by making an incredibly precise change—down to a single atom—while largely preserving the structure and stability of the enzyme." The researchers applied the approach to PET hydrolases, commonly known as PETases, which are enzymes capable of breaking down PET into its component molecules.
These enzymes have already undergone extensive optimization using computational design and protein engineering. The team introduced noncanonical amino acids called azatryptophans, which closely resemble the naturally occurring amino acid tryptophan except for the substitution of a carbon-hydrogen group with a nitrogen atom. PET-degrading enzymes containing this substitution at a single site proved to break down PET nearly twice as efficiently while maintaining thermal stability.
Abdelkader said the findings challenge the idea that enzyme engineering necessarily requires multiple changes to a protein. "Instead of redesigning an enzyme with many mutations, we can make a very small, targeted change and have a significant effect on how it works," Abdelkader said. The researchers also developed a new rapid fluorescence-based test called PETra, which allows scientists to measure PET-degrading enzyme activity in minutes, rather than hours or days as required by conventional activity tests.
Because PET is insoluble and structurally complex, PETra uses a soluble fluorescent substrate as a PET mimic. The researchers showed that PETra results correlate strongly with how effectively the enzymes break down solid PET, greatly accelerating the screening of future variants of plastic-degrading enzymes. Co-author Professor Thomas Huber said the approach could extend well beyond plastic recycling.
"Proteins are incredibly powerful machines, but we are generally limited to the 20 amino acids found in nature when we engineer them," Huber said. "Building on the team's experience with the site-specific introduction of noncanonical amino acids into proteins, we can introduce tiny chemical changes that allow us to tune proteins with a level of precision that was previously difficult to achieve." The researchers say the same strategy could potentially be applied to engineer enzymes for a wide range of applications, including sustainable manufacturing, biotechnology and medicine. Abdelkader et al, Isosteric Engineering of Enzymes: Overcoming Activity–Stability Trade‐Offs by Site‐Selective CH → N Substitutions, Angewandte Chemie International Edition (2026).
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