Theoretical Studies on the Deacylation Stage of the Hydrolysis of PET Heptamer by PETase

doi:10.1007/s40242-025-5133-6

Abstract

Abstract: The extensive use and excellent durability of polyethylene terephthalate (PET) have caused a surge in plastic waste. The discovery of the Ideonella sakaiensis PETase (IsPETase) has opened up a promising avenue for PET bio-recycling, as it can effectively depolymerize PET into valuable monomers. In this work, we employed the M06-2X/MM-MD method (MM-MD: molecular mechanics-molecular dynamics) to study the deacylation reaction of a PET heptamer and reveal the structural features that influence the free energy barrier. This reaction proceeds in a stepwise manner, and the first step is rate-limiting. The energy barrier is 20.4 kcal/mol (1 kcal=4.18 kJ), higher than those for other PET substrates with shorter chains, which supports our previous finding that the deacylation becomes difficult with increasing PET chain length. The hydrogen bonds in the oxyanion hole and between His208 and Asp177 play an important role in the reaction mechanism. In addition, PET self-interaction increases the free energy barrier compared with the short oligomers. This work reveals the catalytic mechanism of PETase in degrading long-chain PET, aiming to promote the engineering of a critical class of enzymes in plastic recycling.

Key words: PETase, Biodegradation, Polyethylene terephthalate, Quantum mechanics/molecular mechanics-molecular dynamics (QM/MM-MD)

GUO Xuehui, ZHOU Yanzi, XIE Daiqian. Theoretical Studies on the Deacylation Stage of the Hydrolysis of PET Heptamer by PETase[J]. Chemical Research in Chinese Universities, 2025, 41(5): 1076-1083.

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