ArticleNature communications2023
Tandemly duplicated CYP82Ds catalyze 14-hydroxylation in triptolide biosynthesis and precursor production in Saccharomyces cerevisiae.
Article in Nature communications, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 32 citations in OpenAlex.
- Biosynthesis and heterologous production of the α-agarofuran scaffold of Celangulin V from Celastrus angulatus.Nature communications · 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
- Efficient biosynthesis of the plant-derived diterpenoid 14-hydroxy-dehydroabietadiene in Saccharomyces cerevisiae.Microbial cell factories · 2026Article
- Targeted Delivery of Triptolide Via Folate-Functionalized Pluronic Micelles Enhances Anti-Melanoma Activity by Inducing Reactive Oxygen Species Accumulation.BioMed research international · 2026Article
- Triptolide-mediated immunomodulation of macrophages: from pathophysiology to therapy.Annals of medicine · 2025Review
- Metabolic Engineering of Terpenoid Biosynthesis in Medicinal Plants: From Genomic Insights to Biotechnological Applications.Current issues in molecular biology · 2025Review
- Insights into angiosperm evolution and lineage-specialized lignan biosynthesis from the early-divergingScience advances · 2025Article
- Divergent multifunctional P450s-empowered biosynthesis of bioactive tripterifordin and cryptic atiserenoids in Aconitum implies convergent evolution.Nature communications · 2025Article
- 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
- A long road ahead to reliable and complete medicinal plant genomes.Nature communications · 2025Review
- Engineering the microenvironment of P450s to enhance the production of diterpenoids inActa pharmaceutica Sinica. B · 2024Article
- Integrated transcriptomics and metabolomics provide insights into the biosynthesis of militarine in the cell suspension culture system of Bletilla striata.Advanced biotechnology · 2024Article
- CYP72D19 from Tripterygium wilfordii catalyzes C-2 hydroxylation of abietane-type diterpenoids.Plant cell reports · 2023Article
- Functional Study and Efficient Catalytic Element Mining of CYP76AHs inMolecules (Basel, Switzerland) · 2023Article
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18 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Triptolide is a valuable multipotent antitumor diterpenoid in Tripterygium wilfordii, and its C-14 hydroxyl group is often selected for modification to enhance both the bioavailability and antitumor efficacy. However, the mechanism for 14-hydroxylation formation remains unknown. Here, we discover 133 kb of tandem duplicated CYP82Ds encoding 11 genes on chromosome 12 and characterize CYP82D274 and CYP82D263 as 14-hydroxylases that catalyze the metabolic grid in triptolide biosynthesis. The two CYP82Ds catalyze the aromatization of miltiradiene, which has been repeatedly reported to be a spontaneous process. In vivo assays and evaluations of the kinetic parameters of CYP82Ds indicate the most significant affinity to dehydroabietic acid among multiple intermediates. The precursor 14-hydroxy-dehydroabietic acid is successfully produced by engineered Saccharomyces cerevisiae. Our study provides genetic elements for further elucidation of the downstream biosynthetic pathways and heterologous production of triptolide and of the currently intractable biosynthesis of other 14-hydroxyl labdane-type secondary metabolites.
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