title: Plant science. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein.
abstract: Morphinan alkaloids from the opium poppy are used for pain relief. The direction of metabolites to morphinan biosynthesis requires isomerization of (S)- to (R)-reticuline. Characterization of high-reticuline poppy mutants revealed a genetic locus, designated STORR [(S)- to (R)-reticuline] that encodes both cytochrome P450 and oxidoreductase modules, the latter belonging to the aldo-keto reductase family. Metabolite analysis of mutant alleles and heterologous expression demonstrate that the P450 module is responsible for the conversion of (S)-reticuline to 1,2-dehydroreticuline, whereas the oxidoreductase module converts 1,2-dehydroreticuline to (R)-reticuline rather than functioning as a P450 redox partner. Proteomic analysis confirmed that these two modules are contained on a single polypeptide in vivo. This modular assembly implies a selection pressure favoring substrate channeling. The fusion protein STORR may enable microbial-based morphinan production.
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Thilo
authors.initials: T
authors.lastname: Winzer
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Marcelo
authors.initials: M
authors.lastname: Kern
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: King
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Tony R
authors.initials: TR
authors.lastname: Larson
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Roxana I
authors.initials: RI
authors.lastname: Teodor
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Donninger
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.affiliation: Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Adam A
authors.initials: AA
authors.lastname: Dowle
authors.affiliation: Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Jared
authors.initials: J
authors.lastname: Cartwright
authors.affiliation: Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Rachel
authors.initials: R
authors.lastname: Bates
authors.affiliation: Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: David
authors.initials: D
authors.lastname: Ashford
authors.affiliation: Bioscience Technology Facility, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Jerry
authors.initials: J
authors.lastname: Thomas
authors.affiliation: GlaxoSmithKline, 1061 Mountain Highway, Post Office Box 168, Boronia, Victoria 3155, Australia.
authors.forename: Carol
authors.initials: C
authors.lastname: Walker
authors.affiliation: GlaxoSmithKline, 1061 Mountain Highway, Post Office Box 168, Boronia, Victoria 3155, Australia.
authors.forename: Tim A
authors.initials: TA
authors.lastname: Bowser
authors.affiliation: Centre for Novel Agricultural Products, Department of Biology, University of York, York YO10 5DD, UK.
authors.forename: Ian A
authors.initials: IA
authors.lastname: Graham
mesh_terms: D001483:Base Sequence; D044182:Benzylisoquinolines / Q000737:chemistry / Q000378:metabolism*; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D056426:Genetic Loci; D007546:Isoquinolines / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009019:Morphinans / Q000737:chemistry / Q000378:metabolism*; D009154:Mutation; D010084:Oxidation-Reduction; D010207:Papaver / Q000201:enzymology* / Q000235:genetics; D010940:Plant Proteins / Q000235:genetics / Q000378:metabolism*; D000644:Quaternary Ammonium Compounds / Q000737:chemistry / Q000378:metabolism*
chemical_list: D044182:Benzylisoquinolines; D007546:Isoquinolines; D009019:Morphinans; D010940:Plant Proteins; D000644:Quaternary Ammonium Compounds; D003577:Cytochrome P-450 Enzyme System; C003298:reticuline