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However, efficient synthesis of them remains a challenge in organic chemistry. Herein, we report the biocatalytic synthesis of saturated bioisosteres of ortho\u2010substituted benzenes using engineered artificial photoenzymes. The artificial photoenzyme, incorporating genetically encoded unnatural amino acids with benzophenone photosensitizer residue, facilitate the formation of chiral saturated bioisosteres with moderate enantiomeric excess via the energy transfer process. Our results demonstrate the versatility of artificial photoenzymes in mediating new\u2010to\u2010nature reactions that are difficult to achieve with conventional chemical or enzymatic methods.<\/jats:p>","DOI":"10.1002\/chem.202404519","type":"journal-article","created":{"date-parts":[[2025,2,17]],"date-time":"2025-02-17T05:38:21Z","timestamp":1739770701000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Enzymatic Synthesis of Saturated Bioisosteres of Ortho\u2010Substituted Benzenes by Artificial Photoenzyme"],"prefix":"10.1002","volume":"31","author":[{"given":"Yuting","family":"Bai","sequence":"first","affiliation":[{"name":"School of Life Sciences and Health Engineering Jiangnan University  Wuxi 214122 China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhui","family":"Sheng","sequence":"additional","affiliation":[{"name":"School of Life Sciences and Health Engineering Jiangnan University  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