Poppies to produce alternative pharmaceuticals

In aerial parts of the opium poppy, including unripe seed capsules, the analgesic alkaloids morphine and codeine are synthesized from the amino acid tyrosine via multiple enzymatic steps, with reticuline as an intermediate.

Blocking a terminal biosynthesis step leads to complete loss of all morphine-type alkaloids from the poppy latex, and to accumulation of reticuline and methylated reticuline derivatives, which normally do not occur at appreciable levels.

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HairpinRNAi is being used to understand complex metabolic pathways in non-model plants. Alkaloid synthesis in poppies is one example. The enzyme codeinone reductase (COR) converts codeinone to codeine, which is demethylated to morphine. An hairpinRNAi construct designed to target all seven members of the COR gene family yielded transgenic plants displaying varying degrees of diminished morphine production, from 25 to 100 per cent, along with the compensatory accumulation of the morphine precursor reticuline. This result was unexpected because reticuline lies eight steps upstream from morphine.

Allen et al., 2004, Nature Biotechnology 22: 1559-1566.