Papaverine 7-O-demethylase, a novel 2-oxoglutarate/Fe(2+)-dependent dioxygenase from opium poppy.
Opium poppy (Papaver somniferum) produces several pharmacologically important benzylisoquinoline alkaloids including the vasodilator papaverine. Pacodine and palaudine are tri-O-methylated analogs of papaverine, which contains four O-linked methyl groups. However, the biosynthetic origin of pacodine and palaudine has not been established. Three members of the 2-oxoglutarate/Fe(2+)-dependent dioxygenases (2ODDs) family in opium poppy display widespread O-dealkylation activity on several benzylisoquinoline alkaloids with diverse structural scaffolds, and two are responsible for the antepenultimate and ultimate steps in morphine biosynthesis. We report a novel 2ODD from opium poppy catalyzing the efficient substrate- and regio-specific 7-O-demethylation of papaverine yielding pacodine. The occurrence of papaverine 7-O-demethylase (P7ODM) expands the enzymatic scope of the 2ODD family in opium poppy and suggests an unexpected biosynthetic route to pacodine.
Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada.
Scott C
SC
Farrow
Department of Biological Sciences, University of Calgary, Calgary, Alberta T2N 1N4, Canada. Electronic address: pfacchin@ucalgary.ca.
Peter J
PJ
Facchini
D018506:Gene Expression Regulation, Plant; D007501:Iron / Q000378:metabolism*; D007656:Ketoglutaric Acids / Q000378:metabolism*; D008745:Methylation; D010090:Oxidoreductases, O-Demethylating / Q000235:genetics / Q000302:isolation & purification / Q000378:metabolism*; D010207:Papaver / Q000201:enzymology*; D010208:Papaverine / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013237:Stereoisomerism; D013379:Substrate Specificity
D007656:Ketoglutaric Acids; D012333:RNA, Messenger; D010208:Papaverine; D007501:Iron; D010090:Oxidoreductases, O-Demethylating
2-Oxoglutarate/Fe(2+)-dependent dioxygenase; Benzylisoquinoline alkaloid metabolism; Opium poppy; Pacodine; Papaverine