ArticlePloS one2015
Towards Elucidating Carnosic Acid Biosynthesis in Lamiaceae: Functional Characterization of the Three First Steps of the Pathway in Salvia fruticosa and Rosmarinus officinalis.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 72 citations in OpenAlex.
- Phytochemistry, Pharmacological Potential, and Future Prospects of Abietane-Type Diterpenoids From Salvia rosmarinus.Chemistry & biodiversity · 2026Review
- A Review of Plant-Derived Diterpenoid Biosynthesis: From Structural Scaffold Diversity and Lineage-Associated Distribution to Enzyme Mining and Discovery Strategies.Molecules (Basel, Switzerland) · 2026Review
- Article
- Chemoenzymatic Synthesis with Plant Oxidases and Metabolic Engineering Enable Rapid Access to Rare Gibberellins.Journal of the American Chemical Society · 2026Article
- Carnosic Acid and Its Semisynthetic Derivatives as Promising Anticancer Agents.International journal of molecular sciences · 2026Review
- Three cytochrome P450 enzymes consecutively catalyze the biosynthesis of furanoclerodane precursors in Salvia species.Plant communications · 2025Article
- Chemical and transcriptomic analyses of leaf trichomes from Cistus creticus subsp. creticus reveal the biosynthetic pathways of certain labdane-type diterpenoids and their acetylated forms.Journal of experimental botany · 2024Article
- Comparative transcriptomics of two Salvia subg. Perovskia species contribute towards molecular background of abietane-type diterpenoid biosynthesis.Scientific reports · 2024Article
- Sequence-Structure Analysis Unlocking the Potential Functional Application of the Local 3D Motifs of Plant-Derived Diterpene Synthases.Biomolecules · 2024Article
- Miltiradiene Production by Cytoplasmic Metabolic Engineering inMetabolites · 2023Article
- Hydroxylases involved in terpenoid biosynthesis: a review.Bioresources and bioprocessing · 2023Review
- Article
- Structural and mechanistic insights into the precise product synthesis by a bifunctional miltiradiene synthase.Plant biotechnology journal · 2023Article
- Mechanistic analysis for the origin of diverse diterpenes inActa pharmaceutica Sinica. B · 2022Article
- Tanshinones: Leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.Current opinion in plant biology · 2022Review
- Chemical and Biological Characterization of the Anticancer Potency ofPlants (Basel, Switzerland) · 2021Article
- Progress in heterologous biosynthesis of forskolin.Journal of industrial microbiology & biotechnology · 2021Review
- Expansion within the CYP71D subfamily drives the heterocyclization of tanshinones synthesis in Salvia miltiorrhiza.Nature communications · 2021Article
- Boosting the Synthesis of Pharmaceutically Active Abietane Diterpenes inFrontiers in plant science · 2020Article
- Functional characterization of the cytochrome P450 monooxygenase CYP71AU87 indicates a role in marrubiin biosynthesis in the medicinal plant Marrubium vulgare.BMC plant biology · 2019Article
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Authors and funding
18 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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