Conformational Selection in Enzyme-Catalyzed Depolymerization of Bio-based Polyesters

Enzymatic degradation of polymers holds promise for advancing towards a bio-based economy. However, the bulky nature of polymers presents challenges in accessibility for biocatalysts, hindering depolymerization reactions. Beyond the impact of crystallinity, polymer chains can reside in different conformations affecting binding efficiency to the enzyme active site. We previously showed that the gauche and trans chain conformers associated with crystalline and amorphous regions of the synthetic polyethylene terephthalate (PET) display different affinity to PETase, thus affecting the depolymerization rate. However, structural-function relationships for biopolymers remain poorly understood in biocatalysis. In this study, we explored the biodegradation of previously synthesized bio-polyesters made from a rigid bicyclic chiral terpene-based diol and copolymerized with various renewable diesters. Herein, four of those polyesters spanning from semi-aromatic to aliphatic were subjected to enzymatic degradations in concert with induced-fit docking (IFD) analyses. The monomer yield following enzymatic depolymerization by IsPETase S238 A, Dura and LCC ranged from 2 % to 17 % without any further pre-treatment step. The degradation efficiency was found to correlate with the extent of matched substrate and enzyme conformations revealed by IFD, regardless of the actual reaction temperature employed. Our findings demonstrate the importance of conformational selection in enzymatic depolymerization of biopolymers. A straight or twisted conformation of the polymer chain is crucial in biocatalytic degradation by showing different affinities to enzyme ground-state conformers. This work highlights the importance of considering the conformational match between the polymer and the enzyme to optimize the biocatalytic degradation efficiency of biopolymers, providing valuable insights for the development of sustainable bioprocesses.