{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,23]],"date-time":"2026-08-23T16:56:20Z","timestamp":1787504180066,"version":"build-2736575974"},"reference-count":84,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,2,14]],"date-time":"2018-02-14T00:00:00Z","timestamp":1518566400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100010663","name":"H2020 European Research Council","doi-asserted-by":"publisher","award":["ERC\u20102012\u2010ADG_20120314"],"award-info":[{"award-number":["ERC\u20102012\u2010ADG_20120314"]}],"id":[{"id":"10.13039\/100010663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Plant Journal"],"published-print":{"date-parts":[[2018,3]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    <jats:italic>Vitex agnus\u2010castus<\/jats:italic>\n                    L. (Lamiaceae) is a medicinal plant historically used throughout the Mediterranean region to treat menstrual cycle disorders, and is still used today as a clinically effective treatment for premenstrual syndrome. The pharmaceutical activity of the plant extract is linked to its ability to lower prolactin levels. This feature has been attributed to the presence of dopaminergic diterpenoids that can bind to dopamine receptors in the pituitary gland. Phytochemical analyses of\n                    <jats:italic>V. agnus\u2010castus<\/jats:italic>\n                    show that it contains an enormous array of structurally related diterpenoids and, as such, holds potential as a rich source of new dopaminergic drugs. The present work investigated the localisation and biosynthesis of diterpenoids in\n                    <jats:italic>V. agnus\u2010castus<\/jats:italic>\n                    . With the assistance of matrix\u2010assisted laser desorption ionisation\u2010mass spectrometry imaging (MALDI\u2010MSI), diterpenoids were localised to trichomes on the surface of fruit and leaves. Analysis of a trichome\u2010specific transcriptome database, coupled with expression studies, identified seven candidate genes involved in diterpenoid biosynthesis: three class II diterpene synthases (diTPSs); three class I diTPSs; and a cytochrome P450 (CYP). Combinatorial assays of the diTPSs resulted in the formation of a range of different diterpenes that can account for several of the backbones of bioactive diterpenoids observed in\n                    <jats:italic>V. agnus\u2010castus<\/jats:italic>\n                    . The identified CYP,\n                    <jats:italic>Vac<\/jats:italic>\n                    CYP76BK1, was found to catalyse 16\u2010hydroxylation of the diol\u2010diterpene, peregrinol, to labd\u201013\n                    <jats:italic>Z<\/jats:italic>\n                    \u2010ene\u20109,15,16\u2010triol when expressed in\n                    <jats:italic>Saccharomyces cerevisiae<\/jats:italic>\n                    . Notably, this product is a potential intermediate in the biosynthetic pathway towards bioactive furan\u2010 and lactone\u2010containing diterpenoids that are present in this species.\n                  <\/jats:p>","DOI":"10.1111\/tpj.13822","type":"journal-article","created":{"date-parts":[[2018,1,10]],"date-time":"2018-01-10T02:36:42Z","timestamp":1515551802000},"page":"943-958","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":88,"title":["Biosynthesis of bioactive diterpenoids in the medicinal plant\n                    <i>Vitex agnus\u2010castus<\/i>"],"prefix":"10.1111","volume":"93","author":[{"given":"Allison M.","family":"Heskes","sequence":"first","affiliation":[{"name":"Plant Biochemistry Laboratory Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"Center for Synthetic Biology \u2018bioSYNergy\u2019 Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"VILLUM Center for Plant Plasticity Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tamil C.M.","family":"Sundram","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"Department of Plant Science Kulliyyah of Science International Islamic University Malaysia 50728 Kuala Lumpur Malaysia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Berin A.","family":"Boughton","sequence":"additional","affiliation":[{"name":"Metabolomics Australia School of BioSciences The University of Melbourne Vic. 3010 Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Niels B.","family":"Jensen","sequence":"additional","affiliation":[{"name":"Evolva A\/S Lers\u00f8 Parkall\u00e9 42\u201044 DK\u20102100 Copenhagen \u00d8 Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolaj L.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"Center for Synthetic Biology \u2018bioSYNergy\u2019 Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"VILLUM Center for Plant Plasticity Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C 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Laboratory Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"Center for Synthetic Biology \u2018bioSYNergy\u2019 Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"VILLUM Center for Plant Plasticity Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bj\u00f6rn","family":"Hamberger","sequence":"additional","affiliation":[{"name":"Plant Biochemistry Laboratory Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C Denmark"},{"name":"Center for Synthetic Biology \u2018bioSYNergy\u2019 Department of Plant and Environmental Sciences University of Copenhagen Thorvaldsensvej 40 DK\u20101871 Frederiksberg C 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