ArticleScience (New York, N.Y.)2015
Six enzymes from mayapple that complete the biosynthetic pathway to the etoposide aglycone.
Article in Science (New York, N.Y.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 192 papers.
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Who cites it
192 citing papers in PubMed, 472 citations in OpenAlex.
- Deciphering podophyllotoxin-mediated defense against downy blight in Litchi chinensis Sonn. via integrated metabolomics and transcriptomics.Molecular horticulture · 2026Article
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- Bacteriophage P22 Virus-Like Particles as Nanoscale Protein Scaffolds for Plant Synthetic Biology.Plant biotechnology journal · 2026Article
- Rank-guided learning accelerates automated enzyme engineering.Nature communications · 2026Article
- Rapid reconstitution and kinase-controlled regulation of algal pyrenoid condensates in engineeredbioRxiv : the preprint server for biology · 2026Article
- Cephalotaxinone enzymes reveal a whole plant model for homoharringtonine biosynthesis.Nature chemical biology · 2026Article
- Transcriptional insights into molecular events occurring during tuber maturation of tigernut (Cyperus esculentus L.).Functional & integrative genomics · 2026Article
- A yeast-based platform for etoposide production via yatein bioconversion.Metabolic engineering communications · 2026Article
- Review
- A single-cell screening platform accelerates functional genetics in plants.Nature biotechnology · 2026Article
- De novo synthesis of plant polyketide plumbagin in yeast: a platform for sustainable production of naphthoquinones.Natural products and bioprospecting · 2026Article
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- Complete biosynthesis of phenylspirodrimanes with unclustered genes inActa pharmaceutica Sinica. B · 2026Article
- Spatial regulation of benzylisoquinoline alkaloid biosynthesis in lotus (Horticulture research · 2026Article
- Synthetic Biology of Plants and Microbes for Agriculture, Environment, and Future Applications.Chemical reviews · 2026Review
- Metabolomics and Transcriptomics Analyses Explore the Genes Related to the Biosynthesis of Antioxidant Active Ingredient Isoquercetin.Foods (Basel, Switzerland) · 2026Article
- Herbgenomics: Unraveling natural product biosynthesis in traditional Chinese medicine.Chinese herbal medicines · 2026Article
- Metabolic engineering strategies for optimized lignan production in plants.Frontiers in plant science · 2026Review
- Integrated biosynthesis of the lignan (-)-pluviatolide in resting and growingFrontiers in bioengineering and biotechnology · 2026Article
- Metabolic engineering inaBIOTECH · 2025Review
132 more citing papers are in PubMed but not listed here.
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2 authors at 1 institution in 1 country.
Funding
Abstract
Podophyllotoxin is the natural product precursor of the chemotherapeutic etoposide, yet only part of its biosynthetic pathway is known. We used transcriptome mining in Podophyllum hexandrum (mayapple) to identify biosynthetic genes in the podophyllotoxin pathway. We selected 29 candidate genes to combinatorially express in Nicotiana benthamiana (tobacco) and identified six pathway enzymes, including an oxoglutarate-dependent dioxygenase that closes the core cyclohexane ring of the aryltetralin scaffold. By coexpressing 10 genes in tobacco-these 6 plus 4 previously discovered-we reconstitute the pathway to (-)-4'-desmethylepipodophyllotoxin (the etoposide aglycone), a naturally occurring lignan that is the immediate precursor of etoposide and, unlike podophyllotoxin, a potent topoisomerase inhibitor. Our results enable production of the etoposide aglycone in tobacco and circumvent the need for cultivation of mayapple and semisynthetic epimerization and demethylation of podophyllotoxin.
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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.