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.

Tucker Burgin

Benjamin C. Pollard

Brandon C. Knott

Heather B. Mayes

Michael F. Crowley

John E. McGeehan

Gregg T. Beckham

H. Lee Woodcock

Communications Chemistry

COMMUNICATIONS CHEMISTRY 是 NATURE RESEARCH 的一本开放获取期刊，发表化学科学所有领域的高质量研究、评论和评论。该杂志发表的研究论文代表了重大进展，为专业研究领域带来了新的化学见解。我们还旨在为所有化学家的重要问题提供一个社区论坛，无论其子学科如何。

Communications Chemistry is an open-access journal published by NATURE RESEARCH, dedicated to high-quality research, reviews, and commentaries across all areas of chemical science. The research papers published in this journal represent significant advancements, providing new insights into the field of chemistry. We also aim to offer a community forum for all chemists to discuss important issues, regardless of their sub-discipline.

《Communications Chemistry》是NATURE RESEARCH旗下的一本开放获取期刊，致力于发表化学科学各个领域的高质量研究论文、评论和综述。该期刊所刊登的研究成果代表了重要的科学进展，为专业领域带来了新的化学见解。此外，我们还旨在为所有化学家提供一个讨论重要问题的社区论坛，无论其研究的子学科是什么。

The reaction mechanism of the Ideonella sakaiensis PETase enzyme

The authors use unbiased QM/MM MD simulations to determine optimal mechanistic descriptions of the acylation and deacylation reactions, revealing the rate-limiting step and key interactions within the catalytic triad and Trp185 conformation.

Category	Quartile
化学	2
化学, 化学综合	2

The reaction mechanism of the Ideonella sakaiensis PETase enzyme

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Journal Info

Category	Quartile
CHEMISTRY, MULTIDISCIPLINARY	1