Biosynthetic regulation of the major opiates of Papaver somniferum

Opium poppy, Papaver somniferum, is the sole source of the analgesic alkaloids morphine and codeine as well as thebaine, a precursor for semi-synthetic opiates. T6ODM (thebaine 6-O-demethylase) and CODM (codeine O-demethylase) are dioxygenases involved in morphine biosynthesis and represent promising targets for metabolic engineering of the morphinan alkaloid pathway through reverse genetic screening. An EMS (ethyl methanesulfonate)-mutagenised population of a morphine accumulating cultivar (>4000 plants) was screened for mutations in CODM and T6ODM. Although nonsense mutations were found in both, complete metabolic blocks and codeine and thebaine were not observed owing to the presence of multiple copies of these genes in the genome. Crosses and further mutagenesis were attempted to produce new cultivars of opium poppy with increased yields of codeine and thebaine.