A long sought after gene that is a critical gateway step in the synthesis of the morphinan class of alkaloids, which include the painkiller drugs morphine and codeine, has been discovered.
The gene, called STORR, is only found in poppy species that produce morphinans. The STORR gene evolved when two other genes encoding oxidase and reductase enzymes came together millions of years ago. The resulting gene fusion plays a key role in production of morphine. The researchers hope this will enable the breeding of bespoke 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 yeast.
Whether or not this can compete commercially with plant based production remains to be seen.
The 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.
The naturally occurring opiates of the morphinan class of alkaloids include morphine, codeine and thebaine. Morphine and codeine can be directly used as analgesic 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 antagonist naloxone, which is used to counter the effects of opiate overdose.
The discovery of the STORR gene completes the suite of genes thought to be required for production of morphinans in microbial systems. Plants remain a proven and efficient production system delivering Kg amounts per hectare of active pharmaceutical ingredients (API) at relatively low cost. Discovery of the STORR gene may enable an alternative supply route to be evaluated.
Tim Bowser, Head of R&D for GlaxoSmithKline Australia’s Opiates Division, said, “The discovery of the STORR gene provides us with a new tool for molecular plant breeding, making it faster and easier. GSK are using this discovery to develop bespoke commercial poppy varieties.”
Citation: Thilo Winzer et al., “Morphinan biosynthesis in opium poppy requires a P450-oxidoreductase fusion protein”, Science Express
GlaxoSmithKline Gene Discovery In Poppies Paves Way For Better Painkillers
By News Staff | June 29th 2015 08:00 AM | Print | E-mail
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