Crowding-induced interfacial aggregation underlies enzyme concentration-dependent inhibition during poly(ethylene terephthalate) depolymerization
Year: 2026
Type: preprint
Abstract: Enzymatic depolymerization of poly(ethylene terephthalate) (PET) using PET hydrolases (PETases) offers a sustainable route for plastic recycling, yet high enzyme loadings paradoxically reduce degradation efficiency. The molecular basis of this enzyme concentration-dependent inhibition (ECDI) has remained unresolved. Here, by exploiting host-dependent differences in folding quality of a sequence-identical PETase, we show that ECDI is driven by crowding-induced interfacial aggregation, which progressively destabilizes PET-bound enzymes. By establishing aggregation propensity as a tractable design parameter, we demonstrate a complementary multi-level engineering framework operating at the sequence, folding, and reaction-environment levels that suppresses interfacial aggregation and improves PET depolymerization across multiple PETases. Our findings reveal how enzyme–enzyme interactions can govern catalytic performance at heterogeneous solid–liquid interfaces, providing a mechanistic basis for designing high-performance biocatalytic systems under high-enzyme-loading conditions.
Source: ChemRxiv
Authors: Eon Ji Jo, Byung Hoon Jo
Institution: Gyeongsang National University
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W7213955373