Report

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

See allHide authors and affiliations

Science  29 Jun 2012:
Vol. 336, Issue 6089, pp. 1704-1708
DOI: 10.1126/science.1220757

You are currently viewing the abstract.

View Full Text

Log in to view the full text

Log in through your institution

Log in through your institution

Alkaloid Synthetic Pathway

Noscapine, a nonaddictive alkaloid found in the opium poppy, can be used as a cough suppressant and a tubulin-binding antitumor agent. Winzer et al. (p. 1704, published online 31 May; see the Perspective by DellaPenna and O'Connor) found that a cluster of 10 genes were key to the production of noscapine. Poppies homozygous for this gene cluster produced high levels of noscapine, heterozygous poppies produced low levels of noscapine, and those poppies lacking the gene cluster produced no noscapine. Silencing individual genes in turn and analyzing the accumulation of intermediate metabolites allowed the biosynthetic pathway of noscapine to be elucidated.

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 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.

View Full Text