A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine

Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis...

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Bibliographic Details
Published in:Science (American Association for the Advancement of Science) 2012-06, Vol.336 (6089), p.1704-1708
Main Authors: Winzer, Thilo, Gazda, Valeria, He, Zhesi, Kaminski, Filip, Kern, Marcelo, Larson, Tony R., Li, Yi, Meade, Fergus, Teodor, Roxana, Vaistij, Fabián E., Walker, Carol, Bowser, Tim A., Graham, Ian A.
Format: Article
Language:English
Subjects:
Alkaloids
Anticancer properties
Antineoplastic Agents, Phytogenic - biosynthesis
Biological and medical sciences
Biosynthesis
Capsules
Classical genetics, quantitative genetics, hybrids
Clusters
Cough
Enzymes
Flowers & plants
Fundamental and applied biological sciences. Psychology
Genes
Genes, Plant
Genetics of eukaryotes. Biological and molecular evolution
Genomes
Latex
Libraries
Low level
Molecular Sequence Data
Morphinans
Multigene Family
Narcotics
Noscapine - metabolism
Open reading frames
Papaver - enzymology
Papaver - genetics
Papaver - metabolism
Papaver somniferum
Pharmaceutical sciences
Plant biology
Poppies
Pteridophyta, spermatophyta
Synthesis
Vegetals
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Summary:Noscapine is an antitumor alkaloid from opium poppy that binds tubulin, arrests metaphase, and induces apoptosis in dividing human cells. Elucidation of the biosynthetic pathway will enable improvement in the commercial production of noscapine and related bioactive molecules. Transcriptomic analysis revealed the exclusive expression of 10 genes encoding five distinct enzyme classes in a high noscapine-producing poppy variety, HN1. Analysis of an F₂ mapping population indicated that these genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed that they exist as a complex gene cluster for plant alkaloids. Virus-induced gene silencing resulted in accumulation of pathway intermediates, allowing gene function to be linked to noscapine synthesis and a novel biosynthetic pathway to be proposed.
ISSN:0036-8075
1095-9203
DOI:10.1126/science.1220757