Morphine-free Poppies

BIOCHEMISTRY

Picture a field of poppies and you're quite likely to think of the licit and illicit drugs derived from the unripe seed capsules of the opium pop py (Papaver somniferum). The most abundant of these is morphine--usually. But a mutant strain of poppies developed in Australia doesn't produce any morphine at all.

Australian and German researchers describe a mutant poppy that accumulates the morphine precursors thebaine and oripavine instead of producing morphine or codeine, another drug along the same biosynthetic pathway [Nature, 431, 413 (2004)]. The strain was discovered among the progeny of commercial poppies treated with a mutagen. The treatment appears to have blocked the biosynthetic pathway to morphine by disrupting the enzyme thebaine demethylase. This enzyme normally removes methyl groups from the morphine precursors; the demethylated intermediates then are transformed to morphine via two different routes.

"The new poppy puts all the biosynthetic effort into producing thebaine and oripavine," says study author Philip J. Larkin, a researcher in the Plant Industry Division of CSIRO, an Australian research organization, in Canberra. "The yields of these compounds are very high, and they are the preferred beginning point for the subsequent synthesis in the factory of new-generation painkillers." Such drugs include the powerful analgesics buprenorphine and oxycodone.

Gene expression studies are now showing how the morphine pathway is blocked and are leading to a better understanding of the biosynthetic pathway in normal poppies. "As our knowledge expands, new prospects emerge for tailoring new plants for different pharmaceutical purposes and for increasing the yields of the existing drugs. We already have research plants indicating success in these new opportunities," Larkin says.