ArticleProceedings of the National Academy of Sciences of the United States of America2013
CYP76AH1 catalyzes turnover of miltiradiene in tanshinones biosynthesis and enables heterologous production of ferruginol in yeasts.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 166 papers.
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166 citing papers in PubMed, 379 citations in OpenAlex.
- Biosynthesis and heterologous production of the α-agarofuran scaffold of Celangulin V from Celastrus angulatus.Nature communications · 2026Article
- Cross-stage single-cell and spatial metabolome analyses reveal periderm specialization and tanshinone biosynthesis in Salvia miltiorrhiza roots.The New phytologist · 2026Article
- 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
- Loss and gain: directing the biosynthesis of metabolites in medicinal plants toward specific targets.Science China. Life sciences · 2026Article
- Engineering Salvia miltiorrhiza hairy roots as a scalable platform for high-yield production of paclitaxel and ginsenoside precursors.Plant communications · 2026Article
- The role of taurine in modulating metal accumulation and gene expression under cadmium stress in Glycyrrhiza glabra.BMC plant biology · 2026Article
- Divergent Roles of SmHMGR2 and a Novel SmHMGR5 in Tanshinone Biosynthesis Revealed by CRISPR/Cas9-Mediated Knockout inInternational journal of molecular sciences · 2026Article
- bHLH130 mediates gibberellin signaling to regulate tanshinone biosynthesis inActa pharmaceutica Sinica. B · 2026Article
- The transcriptional regulatory network involved in periderm-specific tanshinones biosynthesis inActa pharmaceutica Sinica. B · 2026Article
- Article
- The Jasmonate-Responsive SmMPK3-SmWRKY33 Module Positively Regulates Tanshinone Biosynthesis in Salvia miltiorrhiza.Plant biotechnology journal · 2026Article
- Diterpenoids in medicinal plants: structure, distribution, biological activities, biosynthesis, and bioengineering prospects.Frontiers in plant science · 2026Review
- Quantitative Trait Locus Mapping and Candidate Gene Analysis of the Contents of Three Tanshinone Components in Salvia miltiorrhiza Bunge.Biochemical genetics · 2025Article
- SmbZIP5 Integrates Abscisic and Jasmonic Acid Signalling to Positively Regulate Tanshinone Biosynthesis in Salvia miltiorrhiza.Plant biotechnology journal · 2025Article
- Multi-combination comparative transcriptome analysis response to MeJA and identifies genes putatively involved in oridonin biosynthesis in Isodon rubescens.BMC plant biology · 2025Article
- Glycyrrhiza, a commonly used medicinal herb: Review of species classification, pharmacology, active ingredient biosynthesis, and synthetic biology.Journal of advanced research · 2025Review
- Molecular mechanism ofHorticulture research · 2025Article
- Multi-omics analysis reveals tissue-specific biosynthesis and accumulation of diterpene alkaloids in Aconitum japonicum.Journal of natural medicines · 2025Article
- Calcium-Induced Regulation ofJournal of fungi (Basel, Switzerland) · 2025Article
- Bacterial biosynthesis of abietane-type diterpene ferruginol from glucose.Microbial cell factories · 2025Article
106 more citing papers are in PubMed but not listed here.
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12 authors at 5 institutions in 2 countries.
Funding
Abstract
Cytochrome P450 enzymes (CYPs) play major roles in generating highly functionalized terpenoids, but identifying the exact biotransformation step(s) catalyzed by plant CYP in terpenoid biosynthesis is extremely challenging. Tanshinones are abietane-type norditerpenoid naphthoquinones that are the main lipophilic bioactive components of the Chinese medicinal herb danshen (Salvia miltiorrhiza). Whereas the diterpene synthases responsible for the conversion of (E,E,E)-geranylgeranyl diphosphate into the abietane miltiradiene, a potential precursor to tanshinones, have been recently described, molecular characterization of further transformation of miltiradiene remains unavailable. Here we report stable-isotope labeling results that demonstrate the intermediacy of miltiradiene in tanshinone biosynthesis. We further use a next-generation sequencing approach to identify six candidate CYP genes being coregulated with the diterpene synthase genes in both the rhizome and danshen hairy roots, and demonstrate that one of these, CYP76AH1, catalyzes a unique four-electron oxidation cascade on miltiradiene to produce ferruginol both in vitro and in vivo. We then build upon the previous establishment of miltiradiene production in Saccharomyces cerevisiae, with incorporation of CYP76AH1 and phyto-CYP reductase genes leading to heterologous production of ferruginol at 10.5 mg/L. As ferruginol has been found in many plants including danshen, the results and the approaches that were described here provide a solid foundation to further elucidate the biosynthesis of tanshinones and related diterpenoids. Moreover, these results should facilitate the construction of microbial cell factories for the production of phytoterpenoids.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.