Scientists at the University of York and GlaxoSmithKline (GSK) Australia have made a key genetic¹ discovery in poppies, paving the way for more effective painkillers³. The discovery, published in the latest issue of Science, reveals the long sought after gene² that is seen as a critical gateway⁵ step in the synthesis of the morphinan class of alkaloids, which include the painkiller⁴ drugs morphine and codeine. 

 

The gene, called STORR, is only found in poppy species that produce morphinans. The STORR gene evolved when two other genes⁶ encoding oxidase and reductase enzymes⁷ came together millions of years ago. The resulting gene fusion⁸ plays a key role in production of morphine. 

 

Scientists hope this will enable the breeding of bespoke⁹ poppy varieties, including those that produce the anti-cancer compound noscapine. Discovery of the STORR gene completes the set of genes needed for genetic engineering of morphine production in microbes such as yeast¹⁰. Whether or not this can compete commercially with plant based production remains¹¹ to be seen.

 

The breakthrough came when scientists identified poppy plants that were not able to produce morphine or codeine but instead accumulated another compound called (S)-reticuline. These plants were found to carry mutations in the STORR gene. These mutations cause a roadblock in the pathway to morphine production in poppy plants. The scientists were able to show that the non-mutated wild type gene can overcome the roadblock, by expressing it in yeast cells.

 

Professor Ian Graham, who led the research in the Centre for Novel Agricultural Products, based in the Department of Biology at the University of York, said: "Plants produce an amazing array of natural chemicals. Discovery of this STORR gene fusion provides us with new insight into how poppy plants have evolved to produce the most effective painkillers known to man".

 

The naturally occurring opiates of the morphinan class of alkaloids include morphine, codeine and thebaine. Morphine and codeine can be directly used as analgesic¹² painkillers. Thebaine is widely used as the starting point for synthesis of a number of semi-synthetic opiates including hydrocodone, hydromorphone, oxycodone, and oxymorphone. Thebaine is also used to synthesise the opioid antagonist¹³ naloxone, which is used to counter the effects of opiate overdose. 

 

Dr Thilo Winzer, lead author on the Science publication, said: "Opium¹⁴ poppy is one of the most important medicinal plants. The formation of the fusion protein was probably a key evolutionary¹⁵ event in its ability to synthesise pharmaceutically¹⁶ important morphinan alkaloids."

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