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Unraveling Entropic Rate Acceleration Induced by Solvent Dynamics in Membrane Enzymes
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Mechanistic insights into modulation of productive substrate accessibility for efficient PET depolymerization.

Dongwoo Ki1, Jiyoung Park2,3, Hwaseok Hong4

  • 1School of Life Sciences, BK21 FOUR KNU Creative BioResearch Group, Kyungpook National University, Daegu, Republic of Korea.

Nature Communications
|June 25, 2026
PubMed
Summary
This summary is machine-generated.

Modifying the surface-exposed C-terminal loop (SEC-loop) of polyethylene terephthalate (PET) hydrolases enhances plastic degradation. This strategy improves enzyme accessibility to PET, boosting depolymerization rates for efficient plastic recycling.

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Area of Science:

  • Biotechnology and Bioengineering
  • Enzyme Engineering
  • Polymer Science

Background:

  • Polyethylene terephthalate (PET) hydrolases are crucial for plastic degradation.
  • Limited understanding of structural factors hindering PETase catalytic efficiency.
  • The surface-exposed C-terminal loop (SEC-loop) in Cryptosporangium aurantiacum PETase (CaPETase) was identified as a potential inhibitor.

Purpose of the Study:

  • To investigate the role of the protruding SEC-loop in CaPETase activity.
  • To engineer CaPETase variants with enhanced PET depolymerization.
  • To assess the broader applicability of SEC-loop modulation for PETase engineering.

Main Methods:

  • Site-directed mutagenesis to replace the protruding SEC-loop with a non-protruding variant.
  • Kinetic analyses to determine enzyme activity and catalytic efficiency.
  • Adsorption studies to evaluate enzyme-substrate interaction and accessibility.

Main Results:

  • The non-protruding SEC-loop variant exhibited significantly enhanced PET depolymerization rates compared to wild-type CaPETase.
  • Kinetic and adsorption studies revealed that the modified SEC-loop promotes productive enzyme-PET access without altering binding affinity.
  • The SEC-loop engineering strategy proved effective across diverse PETase variants, demonstrating broad applicability.

Conclusions:

  • Modulating enzyme accessibility via SEC-loop engineering is a viable strategy for improving PETase performance.
  • This approach offers a novel avenue for rational enzyme design in plastic degradation.
  • Enhanced enzyme accessibility, rather than active site modification alone, can significantly boost PET depolymerization efficiency.