Molecular genetic analysis of an O-methyltransferase of the opium poppy Papaver somniferum

Isoquinoline alkaloids are a large class of compounds derived from the amino acid L-tyrosine containing many physiologically active members. Among the isoquinoline alkaloids, morphine is one of the pharmaceutically important members that is still derived from the plant that produces it, the opium poppy Papaver somniferum. P. somniferum produces over 80 alkaloids derived from L-tyrosine. We have isolated cDNAs encoding several enzymes of tetrahydrobenzylisoquinoline-derived alkaloid biosynthesis from this plant. The first enzyme in the biosynthetic pathway for which we have isolated a cDNA is norcoclaurine 6-O-methyltransferase. The next is the cytochrome P-450-dependent monooxygenase (S)-N-methylcoclaurine 3'-hydroxylase. These enzymes are common to the morphine, noscapine and sanguinarine biosynthetic pathways. Specific to the sanguinarine pathway is the berberine bridge enzyme that oxidatively cyclizes the N-methyl moiety of (S)-reticuline to the bridge carbon C-8 of (S)-scoulerine. Finally, specific to morphine biosynthesis are salutaridinol 7-O-acetyltransferase and codeinone reductase the penultimate enzyme of the morphine pathway that reduces codeinone to codeine. Given the number of cDNAs specific to various alkaloid biosynthetic pathways that we now have, attempts at metabolic engineering of P. somniferum can be made. We describe herein details of the isolation and biochemical characterization of a cDNA encoding the P. somniferum O-methyltransferase OMTPS3.