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Papaverine 7‐ O ‐demethylase, a novel 2‐oxoglutarate/Fe 2+ ‐dependent dioxygenase from opium poppy
Author(s) -
Farrow Scott C.,
Facchini Peter J.
Publication year - 2015
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2015.07.042
Subject(s) - opium poppy , benzylisoquinoline , papaver , papaverine , chemistry , stereochemistry , codeine , noscapine , biosynthesis , alkaloid , biology , biochemistry , morphine , enzyme , botany , pharmacology , endocrinology
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.