Biodegradation Mechanism of Polycaprolactone by a Novel Esterase MGS0156: A QM/MM approach
Nowadays micro-plastics pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastics waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics like polycaprolactone, polylactide, etc. Here a combined Molecular Dynamics, Molecular Mechanics Poisson-Boltzmann Surface Area, and Quantum Mechanics/Molecular Mechanism method were used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from monomer to tetramer), we found that longer oligomer has relatively stronger binding energy. The degradation process involves two concerted elementary steps: triad-assisted nucleophilic attack and C-O bond cleavage. C-O bond cleavage is the rate determining step with an average barrier of 15.7 kcal/mol, which is in consistent with the experimentally determined kcat (1101 s-1, corresponds to 13.3 kcal/mol). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as the potential mutation targets for designing more efficient MGS0156 mutants.