Plant science. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein.

Science (New York, N.Y.) 2015 Jul 17

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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. Copyright © 2015, American Association for the Advancement of Science.

Citation

Thilo Winzer, Marcelo Kern, Andrew J King, Tony R Larson, Roxana I Teodor, Samantha L Donninger, Yi Li, Adam A Dowle, Jared Cartwright, Rachel Bates, David Ashford, Jerry Thomas, Carol Walker, Tim A Bowser, Ian A Graham. Plant science. Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein. Science (New York, N.Y.). 2015 Jul 17;349(6245):309-12