Concentration-Dependent Inhibition of Mesophilic PETases on Poly(ethylene terephthalate) can be Eliminated by Enzyme Engineering

Luisana Avilan, Bruce Lichtenstein, Gerhard Koenig, Michael Zahn, Mark Allen, Liliana Oliveira, Matilda Clark, Victoria Bemmer, Rosie Graham, Harry Austin, Graham Dominick, Christopher Johnson, Gregg Beckham, John McGeehan, Andrew Pickford

Research output: Contribution to journalArticlepeer-review

13 Scopus Citations


Enzyme-based depolymerization is a viable approach for recycling of poly(ethylene terephthalate) (PET). PETase from Ideonella sakaiensis (IsPETase) is capable of PET hydrolysis under mild conditions but suffers from concentration-dependent inhibition. In this study, this inhibition is found to be dependent on incubation time, the solution conditions, and PET surface area. Furthermore, this inhibition is evident in other mesophilic PET-degrading enzymes to varying degrees, independent of the level of PET depolymerization activity. The inhibition has no clear structural basis, but moderately thermostable IsPETase variants exhibit reduced inhibition, and the property is completely absent in the highly thermostable HotPETase, previously engineered by directed evolution, which simulations suggest results from reduced flexibility around the active site. This work highlights a limitation in applying natural mesophilic hydrolases for PET hydrolysis and reveals an unexpected positive outcome of engineering these enzymes for enhanced thermostability.

Original languageAmerican English
Article numbere202202277
Number of pages12
Issue number8
StatePublished - 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. ChemSusChem published by Wiley-VCH GmbH.

NREL Publication Number

  • NREL/JA-2A00-84888


  • biocatalysis
  • hydrolases
  • mesophilic enzymes
  • PETase
  • plastics


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