Bayer_2026_Nat.Chem.Biol__

Stable chemical bonds as well as noncovalent interactions define the properties of industrial chemicals and materials, including polyesters such as polyethylene terephthalate (PET), polyamides (nylons) and polyurethanes. The resistance of plastics to hydrolysis contributes to the global issues of waste accumulation and environmental pollution. Recently identified metagenomic enzymes act on highly stable ester, amide and carbamate bonds in small molecules as well as pretreated polymeric materials. However, depolymerization activities, particularly for nylons and polyurethanes, remain too low to facilitate the efficient treatment of plastic waste. This Perspective highlights the natural diversity of different hydrolase superfamilies suitable for deconstructing synthetic polymers and examines their catalytic features. We also discuss strategies for discovering biocatalysts and tailoring their properties by protein engineering-both assisted by bioinformatics and (ultra)high-throughput screening tools. The combination of these approaches and thorough process analyses will be required to advance hydrolase-based depolymerization of plastics beyond the current recycling schemes for PET.