Enzymatic Synthesis of Poly(caprolactone): A QM/MM Study

Our reliance on synthetic polymers (plastics) is causing immeasurable damage to the environment. Better alternatives are actively being sought-after, such as biodegradable polyesters obtained by enzymatic synthesis. Here we compare in detail the catalytic mechanisms for poly(caprolactone) synthesis by the enzymesArchaeoglobus fulgiduscarboxylesterase (AfEST) andCandida antarcticalipase B (CalB) using Quantum Mechanics/Molecular Mechanics Molecular Dynamics simulations. In the ring-opening step (rate-limiting) the significantly higher free energy barrier found for AfEST is a consequence of the larger distance between the histidine-aspartate pair and the oxygen of the lactone, and a shorter distance to the serine nucleophile, favouring the reverse reaction towards the initial reactants. Our results give important insights towards the design of enzymatic variants which combine high activity and high thermostability in the synthesis of poly(caprolactone), which due to its bioresorbability is of great importance for biomedical applications.