ArticleJournal of the American Chemical Society2019
Total Biosynthesis for Milligram-Scale Production of Etoposide Intermediates in a Plant Chassis.
Article in Journal of the American Chemical Society, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 88 citations in OpenAlex.
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- De novo biosynthesis of plant lignans by synthetic yeast consortia.Nature chemical biology · 2025Article
- Phylogenomics and metabolic engineering reveal a conserved gene cluster in Solanaceae plants for withanolide biosynthesis.Nature communications · 2025Article
- Characterization of a 4'-O-rhamnosyltransferase and de novo biosynthesis of bioactive steroidal triglycosides from Paris polyphylla.Plant communications · 2025Article
- Navigating the challenges of engineering composite specialized metabolite pathways in plants.The Plant journal : for cell and molecular biology · 2025Review
- Cloning and bioinformatics analysis of key gene ShOMT3 of podophyllotoxin biosynthesis pathway in Sinopodophyllum hexandrum.PloS one · 2025Article
- Biochemical evaluation of molecular parts for flavonoid production using plant synthetic biology.Frontiers in plant science · 2025Review
- Unveiling the Power of Flax Lignans: From Plant Biosynthesis to Human Health Benefits.Nutrients · 2024Review
- The Role of Endoplasmic Reticulum Stress on Reducing Recombinant Protein Production in Mammalian Cells.Biochemical engineering journal · 2024Article
- Reconstitution of early paclitaxel biosynthetic network.Nature communications · 2024Article
- The contemporary nexus of medicines security and bioprospecting: a future perspective for prioritizing the patient.Natural products and bioprospecting · 2024Review
- Tailored biosynthesis of diosmin through reconstitution of the flavonoid pathway inFrontiers in plant science · 2024Article
- Genomic consequences associated with Agrobacterium-mediated transformation of plants.The Plant journal : for cell and molecular biology · 2024Review
- Insights into the missing apiosylation step in flavonoid apiosides biosynthesis of Leguminosae plants.Nature communications · 2023Article
- Multiplicity of theACS synthetic biology · 2023Article
- Tunable control of insect pheromone biosynthesis in Nicotiana benthamiana.Plant biotechnology journal · 2023Article
- Applications of synthetic biology in medical and pharmaceutical fields.Signal transduction and targeted therapy · 2023Review
- Current Status and De Novo Synthesis of Anti-Tumor Alkaloids inMetabolites · 2023Review
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Etoposide is a plant-derived drug used clinically to treat several forms of cancer. Recent shortages of etoposide demonstrate the need for a more dependable production method to replace the semisynthetic method currently in place, which relies on extraction of a precursor natural product from Himalayan mayapple. Here we report milligram-scale production of (-)-deoxypodophyllotoxin, a late-stage biosynthetic precursor to the etoposide aglycone, using an engineered biosynthetic pathway in tobacco. Our strategy relies on engineering the supply of coniferyl alcohol, an endogenous tobacco metabolite and monolignol precursor to the etoposide aglycone. We show that transient expression of 16 genes, encoding both coniferyl alcohol and main etoposide aglycone pathway enzymes from mayapple, in tobacco leaves results in the accumulation of up to 4.3 mg/g dry plant weight (-)-deoxypodophyllotoxin, and enables isolation of high-purity (-)-deoxypodophyllotoxin after chromatography at levels up to 0.71 mg/g dry plant weight. Our work reveals that long (>10 step) pathways can be efficiently transferred from difficult-to-cultivate medicinal plants to a tobacco plant production chassis, and demonstrates mg-scale total biosynthesis for access to valuable precursors of the chemotherapeutic etoposide.
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Registered trials
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.