草莓污视频导航

May 28, 2018

Opium poppy plants give up their genetic secrets to 草莓污视频导航-led team

Research led by biochemist Peter Facchini is huge step toward commercializing efficient, yeast-based production of pain-killing opiates
A 草莓污视频导航-led research team, including Xue Chen, Peter Facchini, Jillian Hagel and Limei Chang, has discovered the gene for a new protein crucial for naturally and efficiently producing a compound in opium poppy plants used to make opiate pain-killing drugs.
A 草莓污视频导航-led research team, including Xue Chen, Peter Facchini, Jillian Hagel and Lim Riley Brandt, 草莓污视频导航

A 草莓污视频导航-led research team, including Xue Chen, Peter Facchini, Jillian Hagel and Limei Chang, pictured above,聽has discovered the gene for a new protein crucial for naturally and efficiently producing a compound in opium poppy plants used to make opiate pain-killing drugs.

The team found the gene that encodes a previously unknown protein, an enzyme called thebaine synthase, which plays a vital role in catalyzing the production of thebaine in opium poppies. The discovery is a huge step toward commercializing an efficient, inexpensive yeast-based system for manufacturing opiates such as morphine and codeine, says team leader Peter Facchini, professor of biochemistry in the聽聽in the聽.

鈥淭hebaine is the gateway to all pharmaceutical opiates. This enzyme, thebaine synthase or THS, is essential to achieve commercially viable production levels of thebaine,鈥 says Facchini, who 聽for 26 years has been investigating how the opium poppy plant makes these compounds.

A system using engineered yeast inserted with thebaine-producing genes also could be used to make valuable semi-synthetic pain-killing medications such as oxycodone and hydrocodone, or naloxone and naltrexone which are essential for treating opioid dependency and overdose.

鈥淭he bio-production platform gives you a suite of opportunities to make new compounds that have the same chemical 鈥榖ackbone,鈥 but improved qualities as prescription medicines,鈥 Facchini says.

This includes the potential in the future to produce next-generation pain killers that aren鈥檛 addictive like all currently available opiates, he says.

Much of the research was done by three senior scientists 鈥斅燲ue Chen, Jillian Hagel and Limei Chang 鈥斅爓orking under contact for the 草莓污视频导航 startup聽聽Inc., a Calgary-based biotechnology company. Epimeron was created to commercialize technology developed in Facchini鈥檚 草莓污视频导航 laboratory (he is chief scientific officer and a co-founder along with Hagel).

Several scientists at聽, a San Francisco-based biotechnology firm partnered with Epimeron, also contributed to the research.

鈥淭his is a strong example of entrepreneurship at the 草莓污视频导航,鈥 Facchini says. 鈥淲e continue to demonstrate that you can make groundbreaking discoveries in Calgary, in 聽Alberta, and not only contribute to, but actually lead, an enterprise of crucial importance to the entire world.鈥

The team鈥檚 paper, A Pathogenesis-Related 10 Protein Catalyzes the Final Step in Thebaine Biosynthesis, is published in聽Nature Chemical Biology, a journal in the top-ranked聽狈补迟耻谤别听听series of publications.

The team found the gene that encodes a previously unknown protein, an enzyme called thebaine synthase which plays a vital role in catalyzing the production of thebaine 鈥 the latex in opium poppies.

The team found the gene that encodes a previously unknown protein, the latex in opium poppies.

Riley Brandt, 草莓污视频导航

World dependent on opium poppies for opiates

The opium poppy is the sole source for all opiates used in medicine, and the United Nations and national governments allow crops to be grown in only a few countries.

That makes Canada and the rest of the world dependent on opium poppy crops, about half of which are cultivated in Tasmania, Australia. The remaining crops are grown mostly in India, Turkey and France.

Yields from these crops are always uncertain, due to environmental factors, climate change, disease and pests, Facchini says. 鈥淲hat if there鈥檚 a blight 鈥斅燼nd there have been blights 鈥斅爋f the opium poppy crop in Australia?鈥

Moreover, 95 per cent of the global population has no access to any opiates, he notes. 鈥淗ow do most people in the world manage pain? They don鈥檛.鈥

A production system using yeast grown in a fermenter and fed cheap carbon (sugar) could provide relatively inexpensive opiates to hundreds of millions of people, he says.

The next steps to achieving such a system are to look for any more missing genes involved in thebaine production, and to get plant-derived genes and enzymes to function optimally in a yeast cell.

Team tracked down 鈥榤issing鈥 component in thebaine production

The team started looking for a 鈥榤issing鈥 component in how the opium poppy plant chemically synthesizes thebaine, after observing a problem when trying to produce thebaine in yeast.聽

They found for the first time an unstable, transient compound involved in the final synthesis step which quickly biodegraded into an unwanted byproduct, resulting in very little thebaine produced.

Thebaine accumulates naturally in specialized cells in the latex of the opium poppy plant 鈥斅爐he 鈥渕ilk of the poppy鈥 made famous in the聽Game of Thrones聽television series. The team added some extract from the latex to in vitro assay samples and immediately saw increased thebaine production.

鈥淭hat was really the Eureka! moment, because now you can say there鈥檚 a protein in there that鈥檚 playing that role,鈥 Facchini says.

The team used classic biochemistry techniques such as protein purification, coupled with state-of-the-art proteomics and gene synthesis to pinpoint the gene and its location 鈥斅爄n a novel gene cluster in the opium poppy plant genome.

They then showed the function of thebaine synthase, using 鈥榞ene-silencing鈥 technology to knock down the responsible gene, and an engineered yeast strain with the gene inserted. Even in initial experiments, thebaine production in yeast increased by more than 20-fold. 聽

Epimeron and Intrexon have patented the gene for yeast-based opiate production.

鈥淭he most exciting possibility from this breakthrough work is opening the door to developing new and better opiates,鈥 says Joseph Tucker, CEO of Epimeron.

The team鈥檚 research was supported by Intrexon, Epimeron, the National Research Council of Canada鈥檚聽, Innovate Calgary and the 草莓污视频导航.