Aliphatic Polyester Recognition and Reactivity at the Active Cleft of a Fungal Cutinase.

ABSTRACT: Protein engineering of cutinases is a promising strategy for the biocatalytic degradation of non-natural polyesters. We report a mechanistic study addressing the hydrolysis of the aliphatic polyester poly(butylene succinate, or PBS) by the fungal Apergillus oryzae cutinase enzyme. Through atomistic molecular dynamics simulations and advanced alchemical transformations, we reveal how three units of a model PBS substrate fit the active site cleft of the enzyme, interacting with hydrophobic side chains. The substrate ester moiety approaches the Asp-His-Ser catalytic triad, displaying catalytically competent conformations. Acylation and deacylation hydrolytic reactions were modeled according to a canonical esterase mechanism using umbrella sampling simulations at the quantum mechanical/

SUBMITTER: Vidossich P 

PROVIDER: S-EPMC12076486 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature