Exploring the Reaction Mechanism of Polyethylene Terephthalate Biodegradation through QM/MM Approach
Alberto Santos, Clauber Henrique Souza da Costa, Pedro H. A. Silva, Munir S. Skaf, Jerônimo Lameira
Abstract
High Resolution Image Download MS PowerPoint Slide The enzyme PETase from Ideonella sakaiensis ( Is PETase) strain 201-F6 can catalyze the hydrolysis of polyethylene terephthalate (PET), mainly converting it into mono(2-hydroxyethyl) terephthalic acid (MHET). In this study, we used quantum mechanics/molecular mechanics (QM/MM) simulations to explore the molecular details of the catalytic reaction mechanism of Is PETase in the formation of MHET. The QM region was described with AM1d/PhoT and M06-2 X /6-31+G(d,p) potential. QM/MM simulations unveil the complete enzymatic PET hydrolysis mechanism and identify two possible reaction pathways for acylation and deacylation steps. The barrier obtained at M06-2 X /6-31+G(d,p)/MM potential for the deacylation step corresponds to 20.4 kcal/mol, aligning with the experimental value of 18 kcal/mol. Our findings indicate that deacylation is the rate-limiting step of the process. Furthermore, per-residue interaction energy contributions revealed unfavorable contributions to the transition state of amino acids located at positions 200–230, suggesting potential sites for targeted mutations. These results can contribute to the development of more active and selective enzymes for PET depolymerization.