Programmable biodegradation: Lipase-driven microplastic degradation via AI and omics.

Microplastic pollution is a pervasive global challenge, with millions of tons of plastic entering terrestrial and aquatic ecosystems each year and persisting across diverse environmental compartments. Conventional physical and chemical remediation strategies remain energy-intensive and inefficient, highlighting the need for scalable biological alternatives. Here, we synthesize recent advances in lipase-mediated degradation of ester-bond-containing plastics and propose a unifying framework for programmable biodegradation, in which enzyme activity, substrate accessibility, and downstream metabolism are systematically coordinated. Lipases (EC 3.1.1.3) can hydrolyze synthetic polyesters, including polyethylene terephthalate (PET), polyurethane (PU), polylactide (PLA), and polycaprolactone (PCL), but their performance is constrained by polymer crystallinity, limited environmental stability, and restricted substrate specificity. Integrating insights from multi-omics discovery, artificial intelligence-guided enzyme engineering, and systems-level design reveals emerging strategies to enhance catalytic efficiency and environmental robustness. Although engineered enzyme systems can achieve high depolymerization and monomer recovery under controlled conditions, translation to real environments remains limited by diffusion constraints, enzyme inactivation, and regulatory considerations. Reframing plastic degradation as a multi-scale, designable system rather than a single-enzyme process highlights opportunities for coupling protein engineering with controlled deployment, including biofilm-based localization and metabolic pathway integration, to enable more effective and environmentally relevant microplastic remediation.