{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:51:47Z","timestamp":1760316707523,"version":"build-2065373602"},"reference-count":14,"publisher":"Wiley","issue":"14","license":[{"start":{"date-parts":[[2025,6,23]],"date-time":"2025-06-23T00:00:00Z","timestamp":1750636800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2025,7,18]]},"abstract":"<jats:p>Ephedra alkaloids possess some of the most basic structures of alkaloids. Despite their importance for human use and their commercial relevance, the biosynthesis of ephedra alkaloids has remained enigmatic. The predominant biosynthetic pathway in the literature proposes a thiamin\u2010dependent carboligation followed by a transaminase, although no candidate enzymes have yet been identified in ephedra alkaloid producers. In this work, an alternative pathway in plants to ephedra alkaloids via (<jats:italic>S<\/jats:italic>)\u2013cathinone is investigated that circumvents the formation of 1\u2010phenylpropane\u20101,2\u2010dione as an intermediate and is in full agreement with previous biosynthetic studies. This alternative pathway involves the pyridoxal phosphate (PLP)\u2010dependent carboligation of \u2013benzoyl\u2010CoA\u2013 and <jats:sc>L<\/jats:sc>\u2010alanine in a single step. The PLP\u2010dependent formation of labeled and unlabeled (<jats:italic>S<\/jats:italic>)\u2013cathinone is detected in the plant lysate of young stem tissue of various <jats:italic>Ephedra<\/jats:italic> species that contain Ephedra alkaloids, as well as in young leaf tissue of <jats:italic>Catha edulis<\/jats:italic>. The incorporation of labeled nitrogen from <jats:sc>L<\/jats:sc>\u2010alanine into (<jats:italic>S<\/jats:italic>)\u2010cathinone supports the hypothesis that an \u03b1\u2010oxoamine synthase (AOS) catalyzes the formation of (<jats:italic>S<\/jats:italic>)\u2010cathinone, bypassing the dione as an intermediate. These results demonstrate the involvement of a PLP\u2010dependent AOS as a pivotal step in the biosynthesis of ephedra alkaloids.<\/jats:p>","DOI":"10.1002\/cbic.202500279","type":"journal-article","created":{"date-parts":[[2025,5,1]],"date-time":"2025-05-01T12:28:38Z","timestamp":1746102518000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Biosynthesis of Ephedrine Initiated by Pyridoxal Phosphate\u2010Dependent Formation of Cathinone"],"prefix":"10.1002","volume":"26","author":[{"given":"Karina","family":"Witte","sequence":"first","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstrasse 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Behrens","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstrasse 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hannes M.","family":"Schwelm","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine Forensic Toxicology Medical Faculty \u2010 University of Freiburg  79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Volker","family":"Auw\u00e4rter","sequence":"additional","affiliation":[{"name":"Institute of Forensic Medicine Forensic Toxicology Medical Faculty \u2010 University of Freiburg  79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Institute of Pharmaceutical Sciences University of Freiburg  Albertstrasse 25 79104 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,6,23]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tplants.2012.03.004"},{"key":"e_1_2_5_3_1","doi-asserted-by":"crossref","unstructured":"N. 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