How Many Genes Does It Take To Make A Single Opium Molecule?
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    Unlike the alkaloids morphine and codeine, which are also found in the opium poppy, noscapine is not an addictive analgesic. A close look at its structure reveals why: although a tertiary nitrogen is present, the molecule contains neither a quaternary carbon (a carbon attached to four carbons) nor its associated stereochemistry. 

    One hundred and thirty seven years after its discovery by Pierre Jean Robiquet, who also discovered codeine and asparagus' asparagine--the first amino acid-- someone realized the noscapine is a cough suppressant. Thirty four years after that, in 1998, it was found that noscapine can also induce a suicide reaction on a number of cancer cell lines. This property has inspired more research, including the recent discovery that ten genes are responsible for its biosynthesis.

    Ten genes may seem excessive if one over-focuses on the fact that one defective gene is all it takes to cause colorblindness. But a gene only codes for one protein, and the multi-step production of noscapine requires several enzymes, so not surprisingly, several segments of DNA play a role.

    To make use of the polymerase chain reaction to generate enough DNA for the analysis, Australian investigators turned to nearby Tasmania, where three different varieties of opium have been developed for the purposes of alkaloid production. Through the poppy straw technique, Tasmania produces about 40% of the world's legal opiates using varieties of Papaver somniferum that are carefully selected for high alkaloid content.   

    One type's capsules is rich in morphine; the second is endowed with thebaine, a precursor to synthetic opioids; and noscapine is only found in the third variety along with genes that are absent from the first two types.  Investigators generated an F2 mapping population of 271 individuals using the noscapine variety and the more morphine-rich plants. If the plants did not inherit the 10-gene cluster, they produced very little noscapine.

    To gain insight into the exact steps leading to the production of the anticancer drug, viruses were used to silence six individual genes from this cluster in poppy seedlings, and they were subsequently analyzed for metabolites. This led to elucidation of the following pathway, and the name of the associated gene is placed next to each reaction arrow:


    Science May 31, 2012  A Papaver somniferum 10-Gene Cluster for Synthesis of the Anticancer Alkaloid Noscapine

    Thilo Winzer,1 Valeria Gazda,1 Zhesi He,1 Filip Kaminski,1 Marcelo Kern,1 Tony R. Larson,1 Yi Li,1 Fergus Meade,1 Roxana Teodor,1 Fabián E. Vaistij,1 Carol Walker,2 Tim A. Bowser,2 Ian A. Graham1 


    A scheme, perhaps worthy of Daedalus in the New Scientist:

    Grow large fields of poppies producing noscapine rather than morphine, collect their pollen, and then release masses of bees loaded with this pollen into lawless opium-growing areas.
    Robert H. Olley / Quondam Physics Department / University of Reading / England
    I was under the impression that the variety of opium that was rich in noscapine still produced morphine.