ArticlePloS one2014
Cloning and characterization of a norbelladine 4'-O-methyltransferase involved in the biosynthesis of the Alzheimer's drug galanthamine in Narcissus sp. aff. pseudonarcissus.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 99 citations in OpenAlex.
- A chromosome-level genome assembly of Lycoris radiata reveals the evolutionary origin of Amaryllidaceae alkaloids and elucidates the complete galanthamine biosynthetic pathway.Plant communications · 2026Article
- Amaryllidaceae Alkaloids and Isoquinoline Alkaloids: A Perspective on Historical Approaches to Pathway Elucidation.Plants (Basel, Switzerland) · 2026Review
- Amaryllidaceae Alkaloids and Phenolic Acids Identification inMolecules (Basel, Switzerland) · 2026Article
- Elucidating the enzyme network driving Amaryllidaceae alkaloids biosynthesis in Leucojum aestivum.Plant biotechnology journal · 2025Article
- Alkaloid Profile, Anticholinesterase and Antioxidant Activities, and Sexual Propagation inPlants (Basel, Switzerland) · 2025Article
- Biosynthesis of plant neuroactive alkaloids treating Alzheimer's disease.Frontiers in pharmacology · 2025Article
- Navigating Amaryllidaceae alkaloids: bridging gaps and charting biosynthetic territories.Journal of experimental botany · 2025Review
- Medicinal compounds and biotechnology of Amaryllidaceae alkaloids inFrontiers in plant science · 2025Review
- A developmental gradient reveals biosynthetic pathways to eukaryotic toxins in monocot geophytes.Cell · 2024Article
- Tissue-Specific Natural Synthesis of GalanthamineinPlants (Basel, Switzerland) · 2024Article
- Engineering cascade biocatalysis in whole cells for syringic acid bioproduction.Microbial cell factories · 2024Article
- The Anti-Cholinesterase Potential of Fifteen Different Species ofLife (Basel, Switzerland) · 2024Article
- Biosensor and machine learning-aided engineering of an amaryllidaceae enzyme.Nature communications · 2024Article
- Functional characterization of CYP96T1-like cytochrome P450 fromFrontiers in plant science · 2024Article
- Characterization of norbelladine synthase and noroxomaritidine/norcraugsodine reductase reveals a novel catalytic route for the biosynthesis of Amaryllidaceae alkaloids including the Alzheimer's drug galanthamine.Frontiers in plant science · 2023Article
- Functional Diversification and Structural Origins of Plant Natural Product Methyltransferases.Molecules (Basel, Switzerland) · 2022Review
- Methyltransferases: Functions and Applications.Chembiochem : a European journal of chemical biology · 2022Review
- Biotechnological Approaches to Optimize the Production of Amaryllidaceae Alkaloids.Biomolecules · 2022Review
- Transcriptome analysis of Leucojum aestivum and identification of genes involved in norbelladine biosynthesis.Planta · 2022Article
- Article
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Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Galanthamine is an Amaryllidaceae alkaloid used to treat the symptoms of Alzheimer's disease. This compound is primarily isolated from daffodil (Narcissus spp.), snowdrop (Galanthus spp.), and summer snowflake (Leucojum aestivum). Despite its importance as a medicine, no genes involved in the biosynthetic pathway of galanthamine have been identified. This absence of genetic information on biosynthetic pathways is a limiting factor in the development of synthetic biology platforms for many important botanical medicines. The paucity of information is largely due to the limitations of traditional methods for finding biochemical pathway enzymes and genes in non-model organisms. A new bioinformatic approach using several recent technological improvements was applied to search for genes in the proposed galanthamine biosynthetic pathway, first targeting methyltransferases due to strong signature amino acid sequences in the proteins. Using Illumina sequencing, a de novo transcriptome assembly was constructed for daffodil. BLAST was used to identify sequences that contain signatures for plant O-methyltransferases in this transcriptome. The program HAYSTACK was then used to identify methyltransferases that fit a model for galanthamine biosynthesis in leaf, bulb and inflorescence tissues. One candidate gene for the methylation of norbelladine to 4'-O-methylnorbelladine in the proposed galanthamine biosynthetic pathway was identified. This methyltransferase cDNA was expressed in E. coli and the protein purified by affinity chromatography. The resulting protein was found to be a norbelladine 4'-O-methyltransferase (NpN4OMT) of the proposed galanthamine biosynthetic pathway.
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