ArticleThe Plant journal : for cell and molecular biology2018
Identification and functional characterization of diterpene synthases for triptolide biosynthesis from Tripterygium wilfordii.
Article in The Plant journal : for cell and molecular biology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 66 citations in OpenAlex.
- 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
- Efficient biosynthesis of the plant-derived diterpenoid 14-hydroxy-dehydroabietadiene in Saccharomyces cerevisiae.Microbial cell factories · 2026Article
- Targeted metabolic engineering of key biosynthetic genes improves triptolide production in Tripterygium wilfordii hairy roots.Plant cell reports · 2025Article
- Genome-wide characterization and expression analysis of WRKY family genes in the biosynthesis of triptolide in Tripterygium wilfordii.BMC genomics · 2025Article
- The Pursuit of a Hydroxylation Switch Uncovers a Key Residue for Various Product Outcomes in theOrganic letters · 2025Article
- 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
- Plant (di)terpenoid evolution: from pigments to hormones and beyond.Natural product reports · 2023Review
- Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae.Nature communications · 2023Article
- Structural and mechanistic insights into the precise product synthesis by a bifunctional miltiradiene synthase.Plant biotechnology journal · 2023Article
- The Current Developments in Medicinal Plant Genomics Enabled the Diversification of Secondary Metabolites' Biosynthesis.International journal of molecular sciences · 2022Review
- Tripterygium wilfordii cytochrome P450s catalyze the methyl shift and epoxidations in the biosynthesis of triptonide.Nature communications · 2022Article
- Mechanistic analysis for the origin of diverse diterpenes inActa pharmaceutica Sinica. B · 2022Article
- Diterpene synthases from Leonurus japonicus elucidate epoxy-bridge formation of spiro-labdane diterpenoids.Plant physiology · 2022Article
- Origin and early evolution of the plant terpene synthase family.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Identification of (-)-bornyl diphosphate synthase fromSynthetic and systems biotechnology · 2022Article
- Identification and functional characterization of a PDR transporter in Tripterygium wilfordii Hook.f. that mediates the efflux of triptolide.Plant molecular biology · 2021Article
- MYC2 Transcription Factors TwMYC2a and TwMYC2b Negatively Regulate Triptolide Biosynthesis inPlants (Basel, Switzerland) · 2021Article
- Isolation and Functional Characterization of the Promoters of Miltiradiene Synthase Genes,Plants (Basel, Switzerland) · 2021Article
- Bornyl Diphosphate Synthase FromFrontiers in bioengineering and biotechnology · 2021Article
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Authors and funding
15 authors at 5 institutions in 3 countries.
Funding
Abstract
Tripterygium wilfordii, which has long been used as a medicinal plant, exhibits impressive and effective anti-inflammatory, immunosuppressive and anti-tumor activities. The main active ingredients are diterpenoids and triterpenoids, such as triptolide and celastrol, respectively. A major challenge to harnessing these natural products is that they are found in very low amounts in planta. Access has been further limited by the lack of knowledge regarding their underlying biosynthetic pathways, particularly for the abeo-abietane tri-epoxide lactone triptolide. Here suspension cell cultures of T. wilfordii were found to produce triptolide in an inducible fashion, with feeding studies indicating that miltiradiene is the relevant abietane olefin precursor. Subsequently, transcriptome data were used to identify eight putative (di)terpene synthases that were then characterized for their potential involvement in triptolide biosynthesis. This included not only biochemical studies which revealed the expected presence of class II diterpene cyclases that produce the intermediate copalyl diphosphate (CPP), along with the more surprising finding of an atypical class I (di)terpene synthase that acts on CPP to produce the abietane olefin miltiradiene, but also their subcellular localization and, critically, genetic analysis. In particular, RNA interference targeting either both of the CPP synthases, TwTPS7v2 and TwTPS9v2, or the subsequently acting miltiradiene synthase, TwTPS27v2, led to decreased production of triptolide. Importantly, these results then both confirm that miltiradiene is the relevant precursor and the relevance of the identified diterpene synthases, enabling future studies of the biosynthesis of this important bioactive natural product.
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