Depolymerase-Catalyzed Polyethylene Terephthalate Hydrolysis: A Unified Mechanism Revealed by Quantum Mechanics/Molecular Mechanics Analysis

The exponential growth of polyethylene terephthalate (PET) plastic waste has caused global environmental problems. Enzymatic transformation has become an emerging and promising strategy for PET depolymerization and recycling. Here, we systematically explored the catalytic mechanism of five representative enzymes, namely, IsPETase, RgPETase, BurPL, PET2, and LCC, and evidenced that they all follow the same process which involves four concerted steps. The calculated average energy barriers for these enzymes are 16.2, 15.8, 13.1, 14.5, and 14.1 kcal/ mol, respectively. A dynamic hydrogen-bond network was identified to regulate the PET depolymerization process for all of the investigated enzymes. In addition, the correlations between vital structural/charge features and energy barriers were screened, and key features (e.g., charge Ser@O1, angle PET@C1−H₂O@O3−H₂O@H3) that significantly impact enzyme efficiency were identified. We clarify that the originally proposed structural features like Ser@O1-PET@C1 are not likely to be the dominating features that influence the enzyme efficiency. These new insights collectively offer a key basis for a rational enzyme engineering strategy for benefits of environmental sustainability and production of value-added products.