Enzymatic PET depolymerization: a review of engineering biocatalysts and systems for efficient plastic deconstruction.

The ever-increasing accumulation of polyethylene terephthalate (PET) waste poses a severe threat to global ecosystems and human health. Biological upcycling (integrating enzymatic depolymerization with microbial conversion of the resulting monomers) has emerged as a promising approach to overcome the limitations of traditional mechanical and chemical recycling. This review provides a systematic and critical synthesis of recent advances in PET bio-upcycling, covering the period from 2016 to 2026. We first discuss the discovery, classification, structural features, and catalytic mechanisms of PET-hydrolyzing enzymes, highlighting the rate-limiting constraints imposed by glass transition temperature, substrate crystallinity, interfacial interactions, and product inhibition. We then evaluate protein engineering strategies that have dramatically enhanced thermostability, substrate binding, and multi-enzyme synergy, yielding benchmark variants capable of near-complete depolymerization of post-consumer PET within hours to days. Concurrent innovations in whole-cell biocatalysis, enzyme immobilization, surface display, and microbial consortia are examined, with emphasis on how metabolic division of labor and substrate channeling can alleviate product inhibition and process mixed plastic waste. We also summarize metabolic engineering efforts that have enabled conversion of PET-derived terephthalic acid (TPA) and ethylene glycol (EG) into more than 25 value-added products, including biopolymers, platform chemicals, pharmaceuticals, and specialty compounds. Finally, we discuss remaining technological barriers, economic feasibility, and future frontiers (including computational enzyme design, synthetic consortia, tandem chemo-biological processes, and industrial-scale demonstration) and propose a phased roadmap for industrial translation. This review aims to provide a comprehensive resource for advancing PET bio-upcycling from laboratory innovation toward practical implementation in a circular plastics economy.