ArticlePloS one2017
Biosynthesis of the oxygenated diterpene nezukol in the medicinal plant Isodon rubescens is catalyzed by a pair of diterpene synthases.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 20 papers.
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20 citing papers in PubMed.
- Discovery of the rosalexin pathway expands the modular network of maize diterpenoid phytoalexins.Research square · 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
- Genome-wide analysis of TPS family reveals kaurene synthase-like genes inFrontiers in plant science · 2026Article
- Integrated miRNAome, transcriptome, and degradome analyses reveal the role of miRNA-mRNA modules in the biosynthesis of oridonin inFrontiers in plant science · 2025Article
- Sequential Separation of Essential Oil Components during Hydrodistillation of Fresh Foliage from AzoreanPlants (Basel, Switzerland) · 2024Article
- From functional plasticity of two diterpene synthases (IrTPS2/IrKSL3a) to enzyme evolution.ACS catalysis · 2024Article
- Sequence-Structure Analysis Unlocking the Potential Functional Application of the Local 3D Motifs of Plant-Derived Diterpene Synthases.Biomolecules · 2024Article
- Functional Characterization of Three Diterpene Synthases Responsible for Tetracyclic Diterpene Biosynthesis inPlants (Basel, Switzerland) · 2022Article
- Design, Synthesis and Biological Evaluation of Lophanic Acid Derivatives as Antifungal and Antibacterial Agents.Molecules (Basel, Switzerland) · 2022Article
- Diterpene synthases from Leonurus japonicus elucidate epoxy-bridge formation of spiro-labdane diterpenoids.Plant physiology · 2022Article
- Tanshinones: Leading the way into Lamiaceae labdane-related diterpenoid biosynthesis.Current opinion in plant biology · 2022Review
- The P450 multigene family of Fontainea and insights into diterpenoid synthesis.BMC plant biology · 2021Article
- The foxtail millet (Setaria italica) terpene synthase gene family.The Plant journal : for cell and molecular biology · 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
- A database-driven approach identifies additional diterpene synthase activities in the mint family (Lamiaceae).The Journal of biological chemistry · 2019Article
- Terpene Synthases as Metabolic Gatekeepers in the Evolution of Plant Terpenoid Chemical Diversity.Frontiers in plant science · 2019Review
- Comparative transcriptome analysis of roots, stems and leaves of Isodon amethystoides reveals candidate genes involved in Wangzaozins biosynthesis.BMC plant biology · 2018Article
- Functional Diversity of Diterpene Synthases in the Biofuel Crop Switchgrass.Plant physiology · 2018Article
- Changing Face: A Key Residue for the Addition of Water by Sclareol Synthase.ACS catalysis · 2018Article
- Article
Corrections and comments
- Erratum issued
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4 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Plants produce an immense diversity of natural products (i.e. secondary or specialized metabolites) that offer a rich source of known and potentially new pharmaceuticals and other desirable bioproducts. The Traditional Chinese Medicinal plant Isodon rubescens (Lamiaceae) contains an array of bioactive labdane-related diterpenoid natural products. Of these, the ent-kauranoid oridonin is the most prominent specialized metabolite that has been extensively studied for its potent antimicrobial and anticancer efficacy. Mining of a previously established transcriptome of I. rubescens leaf tissue identified seven diterpene synthase (diTPSs) candidates. Here we report the functional characterization of four I. rubescens diTPSs. IrTPS5 and IrTPS3 were identified as an ent-copalyl diphosphate (CPP) synthase and a (+)-CPP synthase, respectively. Distinct transcript abundance of IrTPS5 and the predicted ent-CPP synthase IrTPS1 suggested a role of IrTPS5 in specialized ent-kaurene metabolism possibly en route to oridonin. Nicotiana benthamiana co-expression assays demonstrated that IrTPS4 functions sequentially with IrTPS3 to form miltiradiene. In addition, IrTPS2 converted the IrTPS3 product (+)-CPP into the hydroxylated tricyclic diterpene nezukol not previously identified in I. rubescens. Metabolite profiling verified the presence of nezukol in I. rubescens leaf tissue. The proposed IrTPS2-catalyzed reaction mechanism proceeds via the common ionization of the diphosphate group of (+)-CPP, followed by formation of an intermediary pimar-15-en-8-yl+ carbocation and neutralization of the carbocation by water capture at C-8 to yield nezukol, as confirmed by nuclear magnetic resonance (NMR) analysis. Oxygenation activity is rare for the family of class I diTPSs and offers new catalysts for developing metabolic engineering platforms to produce a broader spectrum of bioactive diterpenoid natural products.
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