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Drug manufacturing

Enzyme discovery completes morphine biosynthesis pathway

The enzyme that is responsible for converting (S)-reticuline into (R)-reticuline has been discovered. This discovery means safer methods for producing therapeutic alkaloids without the need to cultivate poppy fields. Close-up of an opium poppy, pictured

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Researchers have identified the enzyme that completes the morphine biosynthesis pathway, paving the way for safer methods of producing therapeutic alkaloids without the need to cultivate poppy fields

Researchers have previously succeeded in genetically modifying yeast to make (S)-reticuline, a precursor to a wide range of therapeutic alkaloids including morphine and codeine. Now, a further breakthrough is reported in Science[1] (online, 25 June 2015), with the identification of the enzyme that is responsible for converting (S)-reticuline into (R)-reticuline — the final stage in the morphine biosynthesis pathway.

The newly discovered enzyme, designated STORR [(S)-to-(R)-reticuline], contains a cytochrome P450 module along with oxidoreductase modules, which catalyse the two-step conversion process.

The discovery means that the biosynthetic pathway for morphine is now complete, potentially paving the way for cheaper, safer methods of producing therapeutic alkaloids without the need to cultivate poppy fields. “The fusion protein STORR may enable microbial-based morphinan production,” the researchers say.

Citation: The Pharmaceutical Journal DOI: 10.1211/PJ.2015.20068848

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