Dynamic shift of internal electric field accelerates enzymatic polyethylene terephthalate depolymerization

Enzymatic recycling of polyethylene terephthalate (PET) has been recognized as an eco-friendly option for addressing the global plastic waste problem. Fully deciphering the catalytic mechanism is vital for designing high-performance enzymes. Here, we performed quantum mechanics/molecular mechanics molecular dynamics simulations to systematically explore the depolymerization mechanism of PET by the hydrolase LCC^ICCG. We demonstrate that both PET chain binding and product release require free energy barriers, whereas the rate-determining step corresponds to a catalytic process with a free energy barrier of 20.4 kcal·mol^-1. We also observe that the enzyme internal electric field varies dynamically throughout the catalytic process. Oriented external electric field analysis indicates that this "dynamic shift" stabilizes the transition state more than the reactant, thereby lowering the energy barrier. We anticipate that these insights will contribute to the rational engineering of PET hydrolases by optimizing their dynamic internal electric fields.