A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine.

Thilo Winzer, Valeria Gazda, Zhesi He, Filip Kaminski, Marcelo Kern, Tony R Larson, Yi Li, Fergus Meade, Roxana Teodor, Fabián E Vaistij, Carol Walker, Tim A Bowser, Ian A Graham

Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.

Science (New York, N.Y.) 2012 Jun 29

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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 F(2) 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.

Citation

Thilo Winzer, Valeria Gazda, Zhesi He, Filip Kaminski, Marcelo Kern, Tony R Larson, Yi Li, Fergus Meade, Roxana Teodor, Fabián E Vaistij, Carol Walker, Tim A Bowser, Ian A Graham. A Papaver somniferum 10-gene cluster for synthesis of the anticancer alkaloid noscapine. Science (New York, N.Y.). 2012 Jun 29;336(6089):1704-8