title: CYP719B1 is salutaridine synthase, the C-C phenol-coupling enzyme of morphine biosynthesis in opium poppy.
abstract: Morphine is a powerful analgesic natural product produced by the opium poppy Papaver somniferum. Although formal syntheses of this alkaloid have been reported, the morphine molecule contains five stereocenters and a C-C phenol linkage that to date render a total synthesis of morphine commercially unfeasible. The C-C phenol-coupling reaction along the biosynthetic pathway to morphine in opium poppy is catalyzed by the cytochrome P450-dependent oxygenase salutaridine synthase. We report herein on the identification of salutaridine synthase as a member of the CYP719 family of cytochromes P450 during a screen of recombinant cytochromes P450 of opium poppy functionally expressed in Spodoptera frugiperda Sf9 cells. Recombinant CYP719B1 is a highly stereo- and regioselective enzyme; of forty-one compounds tested as potential substrates, only (R)-reticuline and (R)-norreticuline resulted in formation of a product (salutaridine and norsalutaridine, respectively). To date, CYP719s have been characterized catalyzing only the formation of a methylenedioxy bridge in berberine biosynthesis (canadine synthase, CYP719A1) and in benzo[c]phenanthridine biosynthesis (stylopine synthase, CYP719A14). Previously identified phenol-coupling enzymes of plant alkaloid biosynthesis belong only to the CYP80 family of cytochromes. CYP719B1 therefore is the prototype for a new family of plant cytochromes P450 that catalyze formation of a phenol-couple.
authors: Leibniz-Institut für Pflanzenbiochemie, D-06120 Halle (Saale), Germany.
authors: Andreas
authors: A
authors: Gesell
authors: Megan
authors: M
authors: Rolf
authors: Jörg
authors: J
authors: Ziegler
authors: María Luisa
authors: ML
authors: Díaz Chávez
authors: Fong-Chin
authors: FC
authors: Huang
authors: Toni M
authors: TM
authors: Kutchan
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002384:Catalysis; D002460:Cell Line; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression; D008969:Molecular Sequence Data; D009019:Morphinans / Q000737:chemistry* / Q000378:metabolism; D009020:Morphine / Q000096:biosynthesis* / Q000737:chemistry; D010207:Papaver / Q000201:enzymology* / Q000235:genetics; D010940:Plant Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins; D018411:Spodoptera
chemical_list: D009019:Morphinans; D010940:Plant Proteins; D011994:Recombinant Proteins; D009020:Morphine; C009270:salutaridine; D003577:Cytochrome P-450 Enzyme System