A new Views & Comments article published in Engineering highlights emerging biocatalytic strategies for plastic depolymerization, focusing on artificial intelligence (AI)‑enabled enzyme design and multi‑enzyme cascades as promising routes to enhance sustainable plastic recycling. Global plastic waste has outpaced existing collection and disposal systems, leading to persistent accumulation in terrestrial and aquatic environments and generating micro‑ and nano‑plastics that threaten ecosystems and human health. Conventional recycling approaches, including biodegradable polymers, chemically recyclable polymers, and mechanical and chemical recycling of fossil‑based plastics, face limitations such as high costs, low market penetration, intensive energy use, and secondary pollution. Enzymatic depolymerization has emerged as a mild, specific alternative, operating under aqueous conditions without harsh reagents or high energy inputs, with industrial demonstrations for poly(ethylene terephthalate) (PET) recycling already validated.

The article notes that natural polyesterase–lipase–cutinase‑like hydrolases have approached performance limits in PET depolymerization, with reduced sequence identity to benchmark scaffolds correlating with lower activity. To overcome these constraints, researchers are deploying AI‑driven de novo design to develop novel biocatalysts. Three representative pathways include repurposing a pore‑forming protein into a catalytic nanopore with multiple active sites, constructing serine hydrolases from scratch using computational tools and deep learning evaluation, and refunctionalizing key motifs of leaf–branch compost cutinase onto smaller de novo backbones. These efforts show that AI can reshape the catalytic landscape, yet high performance often relies on structural similarity to natural hydrolases, with challenges remaining in substrate accessibility and recombinant expression.

Multi‑enzyme systems are also advancing to tackle complex plastic substrates. For PET, dual‑enzyme combinations mitigate product inhibition by hydrolyzing soluble intermediates, boosting overall conversion. For polyurethanes, combinations of polyester hydrolases and carbamate hydrolases achieve higher depolymerization levels than single enzymes, with one‑pot systems effective for mixed polyester and polyurethane waste. For non‑hydrolyzable polyolefins, chemo‑enzymatic cascades involving oxidation steps followed by alcohol dehydrogenases and Baeyer–Villiger monooxygenases introduce labile bonds to enable breakdown, supporting upcycling into value‑added chemicals. These systems address interfacial catalysis challenges and broaden the range of treatable plastics, though limitations persist in oxidative enzyme turnover, mass transfer, and cofactor regeneration at scale.

The authors emphasize that biocatalytic innovations will be critical for advancing circular plastic economies. Future work must prioritize scalability, cost‑effectiveness, and compatibility with existing infrastructure, while continuing to develop non‑natural biocatalysts and synergistic multi‑enzyme assemblies. Aligning laboratory advances with industrial feasibility early in development is essential to close polymer life cycles and support a sustainable transition away from linear plastic use.

The paper “New Biocatalytic Approaches for Plastic Depolymerization,” is authored by Ren Wei, Uwe T. Bornscheuer. Full text of the open access paper: https://doi.org/10.1016/j.eng.2025.11.017. For more information about Engineering, visit the website at https://www.sciencedirect.com/journal/engineering.