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These specialized metabolites are also valuable for their antibacterial, anti-spasmolytic, and antitumor activities. We elucidated the complete biosynthetic pathway of these compounds, which starts with the formation of \u03b3-terpinene from geranyl diphosphate. The aromatic backbone of thymol and carvacrol is formed by P450 monooxygenases in combination with a dehydrogenase via an unstable intermediate. Additional P450s hydroxylate thymol and carvacrol to form thymohydroquinone. Our findings demonstrate a mechanism for the formation of phenolic monoterpenes that differs from previous predictions and provides targets for metabolic engineering of high-value terpenes in plants.<\/jats:p>","DOI":"10.1073\/pnas.2110092118","type":"journal-article","created":{"date-parts":[[2021,12,20]],"date-time":"2021-12-20T16:27:11Z","timestamp":1640017631000},"update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":133,"title":["The biosynthesis of thymol, carvacrol, and thymohydroquinone in Lamiaceae proceeds via cytochrome P450s and a short-chain dehydrogenase"],"prefix":"10.1073","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4878-6076","authenticated-orcid":false,"given":"Sandra T.","family":"Krause","sequence":"first","affiliation":[{"name":"Institute of Pharmacy, Department of Pharmaceutical Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907-2063;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2754-3518","authenticated-orcid":false,"given":"Christoph","family":"Crocoll","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Max Planck Institute for Chemical Ecology, 07745 Jena, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2362-2238","authenticated-orcid":false,"given":"Beno\u00eet","family":"Boachon","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Purdue University, West Lafayette, IN 47907-2063;"},{"name":"University of Lyon, UJM-Saint-Etienne, CNRS, BVpam Formation de Recherche en Evolution 3727, 42000 Saint-Etienne, France;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christiane","family":"F\u00f6rster","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Department of Pharmaceutical Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franziska","family":"Leidecker","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Department of Pharmaceutical Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natalie","family":"Wiese","sequence":"additional","affiliation":[{"name":"Institute of Pharmacy, Department of Pharmaceutical Biotechnology, Martin Luther University Halle-Wittenberg, 06120 Halle, Germany;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Plant Biology, Michigan State University, East Lansing, MI 48824;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joshua C.","family":"Wood","sequence":"additional","affiliation":[{"name":"Department of Plant Biology, Michigan State University, East Lansing, MI 48824;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6727-4677","authenticated-orcid":false,"given":"C. 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