The Reaction Mechanism of the Ideonella sakaiensis PETase Enzyme: Article No. 65

Tucker Burgin, Benjamin Pollard, Brandon Knott, Heather Mayes, Michael Crowley, John McGeehan, Gregg Beckham, H. Lee Woodcock

Research output: Contribution to journalArticlepeer-review


Polyethylene terephthalate (PET), the most abundantly produced polyester plastic, can be depolymerized by the Ideonella sakaiensis PETase enzyme. Based on multiple PETase crystal structures, the reaction has been proposed to proceed via a two-step serine hydrolase mechanism mediated by a serine-histidine-aspartate catalytic triad. To elucidate the multi-step PETase catalytic mechanism, we use transition path sampling and likelihood maximization to identify optimal reaction coordinates for the PETase enzyme. We predict that deacylation is likely rate-limiting, and the reaction coordinates for both steps include elements describing nucleophilic attack, ester bond cleavage, and the "moving-histidine" mechanism. We find that the flexibility of Trp185 promotes the reaction, providing an explanation for decreased activity observed in mutations that restrict Trp185 motion. Overall, this study uses unbiased computational approaches to reveal the detailed reaction mechanism necessary for further engineering of an important class of enzymes for plastics bioconversion.
Original languageAmerican English
Number of pages14
JournalCommunications Chemistry
StatePublished - 2024

NREL Publication Number

  • NREL/JA-2800-78219


  • cutinase
  • enzyme mechanism
  • Ideonella sakaiensis
  • plastics
  • poly(ethylene terephthalate)
  • QM/MM simulations
  • serine hydrolase


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