UK scientists discover key poppy alkaloid production enzyme

By Gareth Macdonald

- Last updated on GMT

GSK claims to have identified key enzyme in opium synthesis mechanism
GSK claims to have identified key enzyme in opium synthesis mechanism

Related tags Morphine

GSK and UK academics claim a newly identified enzyme is the missing link in the mechanism poppies use to make painkilling alkaloids like morphine and codeine and the anticancer compound noscapine.

Discovery of the enzyme and the gene that encodes it - STORR - was reported in the journal Science by researchers at the University of York.

Ian Graham from York University told us “The protein product of the STORR gene converts (S)-reticuline to (R)-reticuline in a two-step reaction requiring two separate enzymes, an oxidase and a reductase, that occur as a single protein​.”

Efforts to work out how poppies make alkaloids have accelerated in recent years​ as drugmakers have sought to reduce reliance on a crop that is susceptible to the droughts that strike producers in Tasmania​, Turkey, France and Spain.

However, the York team’s focus is on development of poppies that make noscapine according to Graham, who said: “This will involve identifying plants that contain the genes to make noscapine and are compromised in the activity of the STORR protein. This should block the flow into morphine and direct flow into noscapine​.”

Opiates from yeast

That said, Graham acknowledged the impact the discovery could have on alkaloid production, citing others’ efforts to develop genetically modified (GM) yeast strains​ capable of synthesising morphine.

We are not planning to do this but other groups around the world are. This will involve expressing the STORR gene along with all the other genes involved in morphine production. Proof of concept for this in yeast could be as soon as the next 12 months.

He added that: “It will probably take a lot longer to produce yeasts that make lots of morphine. It will be a major challenge to produce enough to compete with plants as they are extremely efficient at producing lots of morphine at low cost​.” 

The University of York and GSK have filed a patent application relating to this work​” Graham said.

GSK's opiates biz sale on track

GSK used to be a major opium poppy grower in Tasmania.

Last year the firm teamed up with fellow suppliers TPI Enterprises, Tasmanian Alkaloids and J&J to lobby the Australian Government to allow cultivation on the mainland arguing that demand for painkillers coupled with frequent droughts on the island are stretching supplies.

However, in March​ GSK announced its intention to sell its opiates business – including its site in Latrobe, Tasmania and Port Fairy, Victoria – to Indian drugmaker Sun Pharmaceutical Industries. The transaction​ is expected to complete in August.

Source: Science

“Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein” 

Thilo Winzer et al

Related topics Bio Developments Cell lines

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