{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T06:31:44Z","timestamp":1788849104672,"version":"build-2803163510"},"reference-count":80,"publisher":"Wiley","issue":"26","license":[{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T00:00:00Z","timestamp":1778112000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2023YFA0915500"],"award-info":[{"award-number":["2023YFA0915500"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32571652"],"award-info":[{"award-number":["32571652"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32371311"],"award-info":[{"award-number":["32371311"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32201011"],"award-info":[{"award-number":["32201011"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007129","name":"Natural Science Foundation of Shandong Province","doi-asserted-by":"publisher","award":["ZR2025MS282"],"award-info":[{"award-number":["ZR2025MS282"]}],"id":[{"id":"10.13039\/501100007129","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,6,22]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The trifluoromethyl (CF\n                    <jats:sub>3<\/jats:sub>\n                    ) group is a pivotal motif in pharmaceuticals, agrochemicals, and functional materials, yet achieving direct and regioselective aromatic C\u2500H trifluoromethylation\u2014especially for phenols and anilines\u2014remains a formidable challenge. Here, we transform a dual\u2010functional small molecule (DFSM)\u2010facilitated P450BM3 peroxizyme into a versatile biocatalytic platform that enables highly\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010selective trifluoromethylation of diverse phenols and anilines. Through protein engineering, we achieve up to 98%\n                    <jats:italic>ortho<\/jats:italic>\n                    \u2010selectivity for phenol\u2014the first highly selective enzymatic trifluoromethylation reported. The system exhibits broad substrate scope and functional\u2010group tolerance, delivering &gt;99% regioselectivity and over 6700 turnovers for leading substrates. Mechanistic studies confirm a radical pathway and reveal that selectivity is engineered via synergistic mutations\u2010DFSM interactions that pre\u2010organize substrates in a confined active site. This work establishes a programmable strategy to bridge biocatalysis and organofluorine chemistry, offering a sustainable route to valuable fluorinated building blocks.\n                  <\/jats:p>","DOI":"10.1002\/anie.7226888","type":"journal-article","created":{"date-parts":[[2026,5,7]],"date-time":"2026-05-07T10:32:51Z","timestamp":1778149971000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Highly Regioselective Trifluoromethylation of Unprotected Phenols and Anilines Enabled by an Engineered P450 Peroxizyme System"],"prefix":"10.1002","volume":"65","author":[{"given":"Jie","family":"Chen","sequence":"first","affiliation":[{"name":"Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences  Qingdao China"},{"name":"University of Chinese Academy of Sciences  Beijing China"},{"name":"Shandong Energy Institute  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuquan","family":"Yao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qian","family":"Wang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences  Qingdao China"},{"name":"University of Chinese Academy of Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0449-3821","authenticated-orcid":false,"given":"Zhiqi","family":"Cong","sequence":"additional","affiliation":[{"name":"Key Laboratory of Photoelectric Conversion and Utilization of Solar Energy Qingdao New Energy Shandong Laboratory CAS Key Laboratory of Biofuels Shandong Provincial Key Laboratory of Synthetic Biology Qingdao Institute of Bioenergy and Bioprocess Technology Chinese Academy of Sciences  Qingdao China"},{"name":"University of Chinese Academy of Sciences  Beijing China"},{"name":"Shandong Energy Institute  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/pr10102054"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph16081162"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201206566"},{"key":"e_1_2_8_4_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201206566"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr4002879"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm0310333"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.7b01788"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1039\/B610213C"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c01122"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01303"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.0c00996"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.joc.9b01987"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500223h"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500277b"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr1004293"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CS00200G"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1039\/D3QO01603J"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adm8902"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557\u2010023\u201001365\u20100"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c05997"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1039\/D2CC04082D"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature10647"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.4c00303"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.202003143"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201506329"},{"key":"e_1_2_8_25_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201506329"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201801111"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/jo8014825"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.6b01682"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2015.02.034"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.orglett.8b01216"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/asia.202300039"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c10750"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202208936"},{"key":"e_1_2_8_33_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202208936"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202423507"},{"key":"e_1_2_8_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202423507"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.4c14310"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467\u2010025\u201056437\u20101"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.adk8464"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.5c05656"},{"key":"e_1_2_8_39_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.5c02640"},{"key":"e_1_2_8_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms13323"},{"key":"e_1_2_8_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/cr500368h"},{"key":"e_1_2_8_42_1","first-page":"613","article-title":"Emerging Strategies for Modifying Cytochrome P450 Monooxygenases Into Peroxizymes","volume":"57","author":"Fan S.","year":"2024","journal-title":"Accounts of Chemical Research"},{"key":"e_1_2_8_43_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201801592"},{"key":"e_1_2_8_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201801592"},{"key":"e_1_2_8_44_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202311259"},{"key":"e_1_2_8_44_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202311259"},{"key":"e_1_2_8_45_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcat.2023.113618"},{"key":"e_1_2_8_46_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox11030529"},{"key":"e_1_2_8_47_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202215088"},{"key":"e_1_2_8_47_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.202215088"},{"key":"e_1_2_8_48_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC00317H"},{"key":"e_1_2_8_49_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202412100"},{"key":"e_1_2_8_50_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.9b02507"},{"key":"e_1_2_8_51_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0CY00241K"},{"key":"e_1_2_8_52_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.3c00195"},{"key":"e_1_2_8_53_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.4c06342"},{"key":"e_1_2_8_54_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b02709"},{"key":"e_1_2_8_55_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.est.5c08819"},{"key":"e_1_2_8_56_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01256"},{"key":"e_1_2_8_57_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00289\u2010020\u201003419\u20106"},{"key":"e_1_2_8_58_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.9b01508"},{"key":"e_1_2_8_59_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c02068"},{"key":"e_1_2_8_60_1","doi-asserted-by":"publisher","DOI":"10.1021\/acscatal.1c02698"},{"key":"e_1_2_8_61_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021\u20109258(20)82245\u20105"},{"key":"e_1_2_8_62_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20291"},{"key":"e_1_2_8_63_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki464"},{"key":"e_1_2_8_64_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gks375"},{"key":"e_1_2_8_65_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jctc.9b00591"},{"key":"e_1_2_8_66_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.70019"},{"key":"e_1_2_8_67_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.22885"},{"key":"e_1_2_8_68_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20290"},{"key":"e_1_2_8_69_1","doi-asserted-by":"publisher","DOI":"10.1002\/wcms.1121"},{"key":"e_1_2_8_70_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.540130805"},{"key":"e_1_2_8_71_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096\u2010987X(199709)18:12<1463::AID\u2010JCC4>3.0.CO;2\u2010H"},{"key":"e_1_2_8_72_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.464397"},{"key":"e_1_2_8_73_1","doi-asserted-by":"publisher","DOI":"10.1080\/08927029408021981"},{"key":"e_1_2_8_74_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.328693"}],"container-title":["Angewandte Chemie International Edition"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.7226888","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/anie.7226888","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/anie.7226888","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T13:02:23Z","timestamp":1782133343000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/anie.7226888"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,7]]},"references-count":80,"journal-issue":{"issue":"26","published-print":{"date-parts":[[2026,6,22]]}},"alternative-id":["10.1002\/anie.7226888"],"URL":"https:\/\/doi.org\/10.1002\/anie.7226888","archive":["Portico"],"relation":{},"ISSN":["1433-7851","1521-3773"],"issn-type":[{"value":"1433-7851","type":"print"},{"value":"1521-3773","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,7]]},"assertion":[{"value":"2026-02-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-25","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-07","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e7226888"}}