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Currently, the sole reported mirror\u2010image plastic\u2010degrading enzyme, the D\u2010form of 231\u2010residue PET hydrolase ICCG (engineered leaf\u2010branch compost cutinase variant), suffers from thermophilic activity requirements, which limits its practical applications. Here, the first total chemical synthesis of a mirror\u2010image 271\u2010residue D\u2010Fast\u2010PETase was presented by using an enzyme\u2010cleavable solubilizing tag strategy. Comparative kinetic analysis revealed that D\u2010Fast\u2010PETase showed a remarkable increase (\u223c20\u2010fold within 24\u00a0hours) in PET degradation efficiency compared to D\u2010ICCG at temperatures of 37 \u00b0C, making it a promising candidate for prolonged PET decomposition in open environments and holding potential in addressing microplastic\u2010related health issues within the biomedical field. This work not only expands the chemical biology toolbox for mirror\u2010image enzyme synthesis but also establishes D\u2010Fast\u2010PETase as a candidate in combating the dual crises of global plastic pollution and microplastic\u2010associated health risks.<\/jats:p>","DOI":"10.1002\/chem.202501410","type":"journal-article","created":{"date-parts":[[2025,8,26]],"date-time":"2025-08-26T05:15:59Z","timestamp":1756185359000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Chemical Synthesis of the Mirror\u2010Image Fast\u2010PETase by the Enzyme\u2010Cleavable Solubilizing\u2010Tag Strategy"],"prefix":"10.1002","volume":"31","author":[{"given":"Shijun","family":"Zou","sequence":"first","affiliation":[{"name":"Department of Hematology The First Affiliated Hospital of USTC Hefei National Research Center for Interdisciplinary Sciences at the Microscale Center for Advanced Interdisciplinary Science and Biomedicine of IHM 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