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

Science  31 May 2012:

DOI: 10.1126/science.1220757

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Abstract

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 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 the genes are tightly linked in HN1, and bacterial artificial chromosome sequencing confirmed 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.

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