{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T10:52:26Z","timestamp":1790679146537,"version":"4.1.0"},"reference-count":51,"publisher":"Georg Thieme Verlag KG","issue":"08","funder":[{"DOI":"10.13039\/501100001652","name":"Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg","doi-asserted-by":"crossref","award":["Unibund Anschubfinanzierung (JM)"],"award-info":[{"award-number":["Unibund Anschubfinanzierung (JM)"]}],"id":[{"id":"10.13039\/501100001652","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Dr. Hertha and Helmuth Schmauser-Stiftung","award":["Project Funding (JM)"],"award-info":[{"award-number":["Project Funding (JM)"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Planta Med"],"published-print":{"date-parts":[[2023,7]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>3\u03b2-hydroxy-\u03945-steroid dehydrogenases (3\u03b2HSDs) are supposed to be involved in 5\u03b2-cardenolide biosynthesis. Here, a novel 3\u03b2HSD (Dl3\u03b2HSD2) was isolated from Digitalis\n          lanata shoot cultures and expressed in E. coli. Recombinant Dl3\u03b2HSD1 and Dl3\u03b2HSD2 shared 70% amino acid identity, reduced various 3-oxopregnanes and oxidised\n          3-hydroxypregnanes, but only rDl3\u03b2HSD2 converted small ketones and secondary alcohols efficiently. To explain these differences in substrate specificity, we established homology\n          models using borneol dehydrogenase of Salvia rosmarinus (6zyz) as the template. Hydrophobicity and amino acid residues in the binding pocket may explain the difference in enzyme\n          activities and substrate preferences. Compared to Dl3\u03b2HSD1, Dl3\u03b2HSD2 is weakly expressed in D. lanata shoots. High constitutive expression of Dl3\u03b2HSDs was realised by\n          Agrobacterium-mediated transfer of Dl3\u03b2HSD genes fused to the CaMV-35S promotor into the genome of D. lanata wild type shoot cultures. Transformed shoots\n          (35S:Dl3\u03b2HSD1 and 35S:Dl3\u03b2HSD2) accumulated less cardenolides than controls. The levels of reduced glutathione (GSH), which is known to inhibit cardenolide formation, were\n          higher in the 35S:Dl3\u03b2HSD1 lines than in the controls. In the 35S:Dl3\u03b2HSD1 lines cardenolide levels were restored after adding of the substrate pregnane-3,20-dione in\n          combination with buthionine-sulfoximine (BSO), an inhibitor of GSH formation. RNAi-mediated knockdown of the Dl3\u03b2HSD1 yielded several shoot culture lines with strongly reduced\n          cardenolide levels. In these lines, cardenolide biosynthesis was fully restored after addition of the downstream precursor pregnan-3\u03b2-ol-20-one, whereas upstream precursors such as\n          progesterone had no effect, indicating that no shunt pathway could overcome the Dl3\u03b2HSD1 knockdown. These results can be taken as the first direct proof that Dl3\u03b2HSD1 is indeed\n          involved in 5\u03b2-cardenolide biosynthesis.<\/jats:p>","DOI":"10.1055\/a-2074-9186","type":"journal-article","created":{"date-parts":[[2023,5,15]],"date-time":"2023-05-15T22:49:02Z","timestamp":1684190942000},"page":"833-847","source":"Crossref","is-referenced-by-count":6,"title":["Overexpression and RNAi-mediated Knockdown of Two 3\u03b2-hydroxy-\u03945-steroid dehydrogenase Genes in Digitalis lanata Shoot Cultures Reveal Their Role in Cardenolide\n          Biosynthesis"],"prefix":"10.1055","volume":"89","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5875-0248","authenticated-orcid":false,"given":"Tim","family":"Leykauf","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Klein","sequence":"additional","affiliation":[{"name":"Department of Plant Physiology, Friedrich-Schiller-Universit\u00e4t Jena, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Ernst","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Dorfner","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiia","family":"Ignatova","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4239-4349","authenticated-orcid":false,"given":"Wolfgang","family":"Kreis","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Lanig","sequence":"additional","affiliation":[{"name":"National High Performance Computing Center (NHR@FAU), Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9799-8804","authenticated-orcid":false,"given":"Jennifer","family":"Munkert","sequence":"additional","affiliation":[{"name":"Department of Biology, Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg, Erlangen, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2023,5,15]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1093\/cvr\/20.7.516","article-title":"Reduced positive inotropic effects in diseased human ventricular myocardium","volume":"20","author":"L Brown","year":"1986","journal-title":"Cardiovasc Res"},{"key":"ref2","doi-asserted-by":"publisher","first-page":"1932","DOI":"10.3390\/molecules22111932","article-title":"Anticancer and immunogenic properties of cardiac glycosides","volume":"22","author":"N FZ Schneider","year":"2017","journal-title":"Molecules"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"962","DOI":"10.1055\/s-0043-111240","article-title":"The Foxgloves (Digitalis) Revisited","volume":"83","author":"W Kreis","year":"2017","journal-title":"Planta 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