Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and Rosmarinus officinalis

  1. Božić, Dragana
  2. Papaefthimiou, Dimitra
  3. Brückner, Kathleen
  4. de Vos, Ric C. H.
  5. Tsoleridis, Constantinos A.
  6. Katsarou, Dimitra
  7. Papanikolaou, Antigoni
  8. Pateraki, Irini
  9. Chatzopoulou, Fani M.
  10. Dimitriadou, Eleni
  11. Kostas, Stefanos
  12. Manzano, David
  13. Scheler, Ulschan
  14. Ferrer, Albert
  15. Makris, Antonios M.
  16. Kampranis, Sotirios C.
  17. Kanellis, Angelos K.
  18. Tissier, Alain ORCID logo

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WeightNameValue
1000 Titel
  • Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and Rosmarinus officinalis
1000 Autor/in
  1. Božić, Dragana |
  2. Papaefthimiou, Dimitra |
  3. Brückner, Kathleen |
  4. de Vos, Ric C. H. |
  5. Tsoleridis, Constantinos A. |
  6. Katsarou, Dimitra |
  7. Papanikolaou, Antigoni |
  8. Pateraki, Irini |
  9. Chatzopoulou, Fani M. |
  10. Dimitriadou, Eleni |
  11. Kostas, Stefanos |
  12. Manzano, David |
  13. Scheler, Ulschan |
  14. Ferrer, Albert |
  15. Makris, Antonios M. |
  16. Kampranis, Sotirios C. |
  17. Kanellis, Angelos K. |
  18. Tissier, Alain |
1000 Erscheinungsjahr 2015
1000 LeibnizOpen
1000 Publikationstyp
  1. Artikel |
1000 Online veröffentlicht
  • 2015-05-28
1000 Erschienen in
1000 Quellenangabe
  • 10(5):e0124106
1000 FRL-Sammlung
1000 Copyrightjahr
  • 2015
1000 Lizenz
1000 Verlagsversion
  • http://dx.doi.org/10.1371/journal.pone.0124106 |
  • https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4447455/ |
1000 Ergänzendes Material
  • http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0124106#sec025 |
1000 Publikationsstatus
1000 Begutachtungsstatus
1000 Sprache der Publikation
1000 Abstract/Summary
  • Carnosic acid (CA) is a phenolic diterpene with anti-tumour, anti-diabetic, antibacterial and neuroprotective properties that is produced by a number of species from several genera of the Lamiaceae family, including Salvia fruticosa (Cretan sage) and Rosmarinus officinalis (Rosemary). To elucidate CA biosynthesis, glandular trichome transcriptome data of S. fruticosa were mined for terpene synthase genes. Two putative diterpene synthase genes, namely SfCPS and SfKSL, showing similarities to copalyl diphosphate synthase and kaurene synthase-like genes, respectively, were isolated and functionally characterized. Recombinant expression in Escherichia coli followed by in vitro enzyme activity assays confirmed that SfCPS is a copalyl diphosphate synthase. Coupling of SfCPS with SfKSL, both in vitro and in yeast, resulted in the synthesis miltiradiene, as confirmed by 1D and 2D NMR analyses (1H, 13C, DEPT, COSY H-H, HMQC and HMBC). Coupled transient in vivo assays of SfCPS and SfKSL in Nicotiana benthamiana further confirmed production of miltiradiene in planta. To elucidate the subsequent biosynthetic step, RNA-Seq data of S. fruticosa and R. officinalis were searched for cytochrome P450 (CYP) encoding genes potentially involved in the synthesis of the first phenolic compound in the CA pathway, ferruginol. Three candidate genes were selected, SfFS, RoFS1 and RoFS2. Using yeast and N. benthamiana expression systems, all three where confirmed to be coding for ferruginol synthases, thus revealing the enzymatic activities responsible for the first three steps leading to CA in two Lamiaceae genera.
1000 Sacherschließung
lokal Gas-chromatography-mass-spectrometry
lokal Yeast
lokal Hexanes
lokal Polymerase chain reaction
lokal Biosynthesis
lokal Trichomes
lokal Sequence motif analysis
lokal Leaves
1000 Fächerklassifikation (DDC)
1000 Liste der Beteiligten
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1000 Label
1000 Förderer
  1. European Union |
  2. Netherlands Metabolomics Centre |
  3. Cost |
  4. European Commission |
1000 Fördernummer
  1. KBBE-227448
  2. -
  3. FA1006
  4. -
1000 Förderprogramm
  1. TERPMED project
  2. -
  3. -
  4. FP7 post-grant Gold Open Access Pilot
1000 Dateien
1000 Förderung
  1. 1000 joinedFunding-child
    1000 Förderer European Union |
    1000 Förderprogramm TERPMED project
    1000 Fördernummer KBBE-227448
  2. 1000 joinedFunding-child
    1000 Förderer Netherlands Metabolomics Centre |
    1000 Förderprogramm -
    1000 Fördernummer -
  3. 1000 joinedFunding-child
    1000 Förderer Cost |
    1000 Förderprogramm -
    1000 Fördernummer FA1006
  4. 1000 joinedFunding-child
    1000 Förderer European Commission |
    1000 Förderprogramm FP7 post-grant Gold Open Access Pilot
    1000 Fördernummer -
1000 Objektart article
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1000 @id frl:6404923.rdf
1000 Erstellt am 2017-10-11T10:13:58.076+0200
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