This news release is available in Japanese.
Researchers studying poppy plants -- the natural source of pain-relieving alkaloids, such as morphine and codeine -- have identified a fusion gene that facilitates important, back-to-back steps in the plant's morphine-producing pathway. These findings, which build upon recent efforts to engineer the morphine biosynthesis pathway in yeast, complete the metabolic pathway for morphine and pave the way for cheaper, safer routes to producing the economically important drug without the need for cultivating poppy fields. For about a decade, researchers have been trying to put genes into yeast that would allow the microbes to synthesize morphine. Until now, researchers interested in this process had been searching for an enzyme in the morphine biosynthesis pathway that reconfigures the compound known as (S)-reticuline into a variation called (R)-reticuline. By studying mutations in the poppy plant Papaver somniferum, Thilo Winzer and colleagues discovered that the STORR enzyme, expressed by a gene of the same name, catalyzed two related steps, converting (S)-reticuline to an amine, known as 1,2-dehydroreticuline, and then converting that intermediate substrate to (R)-reticuline. The STORR enzyme contains a cytochrome P450 module, which facilitates the first step of the process, along with oxidoreductase modules that facilitate the second step, according to the researchers. Now that the biosynthetic pathway to morphine is complete, researchers can investigate more efficient, microbial-based approaches to opiate-based pain-relievers, which generate billions of dollars in sales each year.
Article #25: "Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein," by T. Winzer; M. Kern; A.J. King; T.R. Larson; R. Teodor; S. Donninger; Y. Li; A.A. Dowle; J. Cartwright; R. Bates; D. Ashford; J. Thomas; I.A. Graham at University of York in York, UK; C. Walker; T.A. Bowser at GlaxoSmithKline in Boronia, VIC, Australia.