Biodegradation mechanism of polycaprolactone by a novel esterase MGS0156: a QM/MM approach

Abstract

Nowadays micro-plastic pollution has become one of the most serious global environmental problems. A potential strategy in managing micro-plastic waste is enzyme-catalyzed degradation. MGS0156 is a hydrolase screened from environmental metagenomes, which can efficiently degrade commercial plastics such as polycaprolactone, polylactide, etc. Here a combined molecular dynamics, molecular mechanics Poisson–Boltzmann surface area, and quantum mechanics/molecular mechanism method was used to reveal the enzymatic depolymerization mechanism. By systematically analyzing the binding processes of nine oligomers (from a monomer to tetramer), we found that longer oligomers have 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⁻¹, which is consistent with the experimentally determined k_cat (1101 s⁻¹, corresponds to 13.3 kcal mol⁻¹). The electrostatic influence analysis of twenty amino acids highlights His231 and Asp237 as potential mutation targets for designing more efficient MGS0156 mutants.