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It exhibits potent immunosuppressive activity, yet its mode of action differs from standard drugs that are currently in use. Further pre\u2010clinical evaluation of this promising, biologically active natural product is hampered by restricted access to the ready material, as its synthesis requires both a low\u2010yielding fermentation process using a pathogenic organism and an elaborate, multi\u2010step total synthesis. Our semi\u2010synthetic approach included a) the heterologous expression of the brasilicardin\u2005A gene cluster in different non\u2010pathogenic bacterial strains producing brasilicardin\u2005A aglycone (<jats:bold>5<\/jats:bold>) in excellent yield and b) the chemical transformation of the aglycone <jats:bold>5<\/jats:bold> into the trifluoroacetic acid salt of brasilicardin\u2005A (<jats:bold>1\u2009a<\/jats:bold>) via a short and straightforward five\u2010steps synthetic route. Additionally, we report the first preclinical data for brasilicardin\u2005A.<\/jats:p>","DOI":"10.1002\/anie.202015852","type":"journal-article","created":{"date-parts":[[2021,3,26]],"date-time":"2021-03-26T08:37:44Z","timestamp":1616747864000},"page":"13536-13541","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Genetic Engineering in Combination with Semi\u2010Synthesis Leads to a New Route for Gram\u2010Scale Production of the Immunosuppressive Natural Product Brasilicardin\u2005A"],"prefix":"10.1002","volume":"60","author":[{"given":"Alma","family":"Botas","sequence":"first","affiliation":[{"name":"Departamento de Biolog\u00eda Funcional e Instituto Universitario de Oncolog\u00eda del Principado de Asturias Universidad de Oviedo and Instituto de Investigaci\u00f3n Sanitaria de Asturias (ISPA)  c\/ Juli\u00e1n Claver\u00eda s\/n. 33006 Oviedo Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Eitel","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Chemistry Institute of Pharmaceutical Sciences University of T\u00fcbingen  Auf der Morgenstelle 8 72076 T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paul N.","family":"Schwarz","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Biotechnology Interfaculty Institute of Microbiology and Infection Medicine University of T\u00fcbingen  Auf der Morgenstelle 28 72076 T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anina","family":"Buchmann","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Biology Institute of Pharmaceutical Sciences University of T\u00fcbingen  Auf der Morgenstelle 8 72076 T\u00fcbingen Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Paula","family":"Costales","sequence":"additional","affiliation":[{"name":"EntreChem S.L. 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