{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T16:00:57Z","timestamp":1790092857034,"version":"4.0.1"},"reference-count":90,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T00:00:00Z","timestamp":1759190400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Angew Chem Int Ed"],"published-print":{"date-parts":[[2026,1,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Amide and thioester moieties are prevalent in pharmaceuticals, natural products, and functional materials, but their chemical synthesis suffers from poor atom economy and ungreen conditions, while biocatalytic methods require ATP\u2010dependent enzymes, activated intermediates, or show limited scope and activity. Here, we report the oxidative coupling of alcohols with ammonia or amines catalyzed by alcohol dehydrogenases (ADHs) via hemiaminal intermediates to form primary and secondary amides at pH 9.5\u201310.5. Pf\u2010ADH preferably converted linear aliphatic or arylaliphatic alcohols (up to 90% conversion), while Pp\u2010ADH and Aa\u2010ADH preferably converted branched or aromatic alcohols (up to 99% conversion). Preparative\u2010scale synthesis of an N\u2010methyl amide gave\u00a0&gt;99% conversion and 87% isolated yield. The method was extended to thioacid and thioester formation via hemithioacetal intermediates using hydrogen sulfide or thiols at pH 7. Pf\u2010ADH favored linear aliphatic alcohols (up to 93% conversion), Pp\u2010ADH branched alcohols (up to 82% conversion), and Aa\u2010ADH aromatic alcohols (up to 98% conversion). A KPi\/MTBE biphasic system enabled the reaction with poorly soluble long\u2010chain thiols. Structure\u2010guided engineering of Aa\u2010ADH led to the Y151A and L186A variants with expanded activity toward longer\u2010chain amines or thiols. This work highlights how enzyme promiscuity with protein engineering can enable new\u2010to\u2010nature synthetic pathways for the production of valuable compounds.<\/jats:p>","DOI":"10.1002\/anie.202515469","type":"journal-article","created":{"date-parts":[[2025,9,30]],"date-time":"2025-09-30T08:30:10Z","timestamp":1759221010000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Amide and Thioester Synthesis Via Oxidative Coupling of Alcohols with Amines or Thiols Using Alcohol Dehydrogenases"],"prefix":"10.1002","volume":"65","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-9135-5916","authenticated-orcid":false,"given":"Matteo","family":"Damian","sequence":"first","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences HIMS\u2010Biocat University of Amsterdam Science Park 904 Amsterdam 1098 XH The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5923-9735","authenticated-orcid":false,"given":"Vasilis","family":"Tseliou","sequence":"additional","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences HIMS\u2010Biocat University of Amsterdam Science Park 904 Amsterdam 1098 XH The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0003-4415-1046","authenticated-orcid":false,"given":"Patrick","family":"Peters","sequence":"additional","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences HIMS\u2010Biocat University of Amsterdam Science Park 904 Amsterdam 1098 XH The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9942-9226","authenticated-orcid":false,"given":"Tanja","family":"Knaus","sequence":"additional","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences HIMS\u2010Biocat University of Amsterdam Science Park 904 Amsterdam 1098 XH The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6771-5102","authenticated-orcid":false,"given":"Francesco G.","family":"Mutti","sequence":"additional","affiliation":[{"name":"Van \u2019t Hoff Institute for Molecular Sciences HIMS\u2010Biocat University of Amsterdam Science Park 904 Amsterdam 1098 XH The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,9,30]]},"reference":[{"key":"e_1_2_7_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.5b01409"},{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/ed1003806"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201003188"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja00284a066"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201308614"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.6b00237"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.6b07230"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.7b00059"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c11260"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.1c02600"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b08415"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1021\/jacs.9b04136"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja2065158"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/ja906005j"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201812227"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202200144"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201006128"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1021\/op500305s"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/acssuschemeng.3c03461"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00712"},{"key":"e_1_2_7_21_1","first-page":"246","volume":"37","author":"Wang N.","year":"2020","journal-title":"Nat. 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