AI Article Synopsis
- Polyethylene terephthalate (PET) can be broken down by the PETase enzyme from Ideonella sakaiensis, with a proposed reaction pathway involving a two-step mechanism using a catalytic triad of serine, histidine, and aspartate.
- Researchers applied transition path sampling and likelihood maximization to identify key reaction coordinates in the PETase catalytic process, predicting that deacylation is the slowest step and involving processes like nucleophilic attack and ester bond cleavage.
- The study highlights the role of Trp185's flexibility in enhancing the reaction speed and offers insights for engineering enzymes that can more effectively convert plastics through bioconversion.
Article Abstract
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.
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|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC10973377 | PMC |
| http://dx.doi.org/10.1038/s42004-024-01154-x | DOI Listing |
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