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  1. Beenthere2Hippie
    The headlines were enough to give anyone a little high. “Home brewed morphine is just around the corner,” “Yeast can make morphine and ‘home-brewed’ heroin” and “Home-brewed heroin could be a thing,” to name just a few.

    Underneath the hyperbolic headlines was the somewhat less-sexy scientific research that prompted them. Scientists have modified yeast to take a molecule of glucose and transform it into the chemical compound (S)-reticuline, a rest stop on the road to eventually producing the opiate morphine. Other scientists have recently tackled the other end of the pathway in different yeast strains. One step remains to bring the two ends together for a process that will eventually result in lab-produced morphine.

    Headlines trumpeted what might happen. In a world where yeast can ferment glucose into morphine, what’s to stop home brewers from perfecting the process of making morphine and then cooking up bathtubs full of heroin? The worries stemmed from an important commentary published May 18 in Nature, alerting scientists to the potential for misuse of the new research, and calling for policies to regulate the future microbes.

    But in all the excitement about regulating home-brewed morphine and heroin, it’s easy to forget one important fact: There isn’t any heroin. And heroin was never the goal in the first place.

    Not a single yeast cell has yet taken a molecule of glucose and produced morphine in return. Instead, scientists have the components of a pathway that, when constructed, could eventually produce an opiate. But the pathway could also be used to produce many other drugs, including potential therapeutics for cancer or new antibiotics. So while it is important to plan ahead and think about regulating an organism that could easily produce large quantities of addictive drugs, it’s also good to keep in mind that any drugs produced from these yeast have far more positive potential than vats of heroin brewed in a bathtub.

    The end goal is the synthesis of benzylisoquinoline alkaloids, or BIAs. This is a large class of chemicals produced in plants such as the poppy, yellowroot and Oregon grape that includes the well-known morphine, heroin — which is synthesized from morphine — and a host of other compounds. These include papaverine, which is used to treat blood vessel spasms, and berberine, which has been tested for lowering blood glucose in diabetes.

    “Most of these molecules are made in vanishingly small amounts naturally,” says John Dueber, a bioengineer at the University of California, Berkeley. And the limited quantities make for limited studies of the chemicals. Getting organisms such as bacteria and yeast to make the target compounds would allow scientists to scale up the productivity of the process.

    Putting the pathway for making those molecules in yeast could also result in a purer product. “The primary function of a plant is not to produce a drug,” explains Pamela Peralta-Yahya, a chemist at the Georgia Institute of Technology in Atlanta. “So purifying [to get the chemical you want] is hard.” If scientists can engineer yeast to perform the process, the organisms could produce far more end product, with far fewer complications. And with yeast, scientists could also introduce new twists in the chemical pathway to synthesize and study new drugs in this class.

    The pathway is almost complete. Dueber’s collaborator Vincent Martin, of Concordia University in Montreal, successfully engineered the steps from (R)-reticuline to codeine and morphine in a study published in PLOS ONE April 23. Another group led by Christina Smolke at Stanford University also published work on the latter half of this pathway in Nature Chemical Biology in 2014. And Dueber and colleagues published the first half of the pathway May 18 in Nature Chemical Biology. Now there’s only one step left, the transformation from (S)-reticuline to (R)-reticuline.

    But that step might be on the way. “It hasn’t been described yet,” Dueber says. “But we believe it’s going to be described very soon.” It will be a several-year process to combine the three pathways together in a single organism, and then make the process efficient enough to achieve measurable levels of morphine or another target compound. In the end, if all goes well, yeast will be able to take in glucose and produce morphine in useful amounts.

    The most recent studies put together all the steps required for yeast to receive glucose and produce morphine. But it is still a proof-of-concept. There is a wide gulf between a series of biological and chemical reactions and a bathtub of yeast fermenting into heroin. Right now, the process is so inefficient that there wouldn’t be any morphine at all. “I should emphasize that even if you put the first part of the pathway with the middle and the end, you would almost certainly not observe any morphine,” Dueber explains. “Each of those pieces has at least one inefficient step. Many challenges need to be solved.”

    But in the meantime, Dueber, Martin and other scientists working on the pathway have approached political scientists with requests to hammer out how the yeast strain might be regulated. Scientific endeavor is slow, but scientific policy is slower. In this case, the policy will have to be international, to reduce the potential for widespread narcotics made from the yeast while keeping the scientific potential intact. Kenneth Oye, a social scientist at MIT, says this means that now is the time, to make sure policies and regulations are considered “with deliberation and not in haste.”

    What Oye wants to avoid is a situation similar to what happened with H5N1 flu. A group of scientists in the Netherlands successfully altered the H5N1 flu strain so that it was transmissible through the air and from mammal to mammal, an exercise carried out to show how few mutations it would take to alter the virus’s transmissibility. When the studies came out, the scientific world panicked and research on the flu strain was temporarily halted. “It went through review at all the institutions with no flags,” Oye recalls. “The issue only came to public attention when Nature and Science were presented with the manuscripts.” Presented with a fait accompli, policymakers were stuck, and “the policies were created in great haste after the fact.”

    All of this is why Dueber, Oye and their colleagues want to think about regulation now. “Might the media provoke policies in haste? I worry about that all the time,” Oye says. But he thinks the possibilities of waiting until the morphine-producing yeast exists are far worse. Better to work on it now, and create careful policies, remembering that while yeast will eventually make morphine, it’s time has not yet arrived.



    By Bethany Brookshire - Science News/June 17, 2015
    https://www.sciencenews.org/blog/scicurious/home-brewed-heroin-hold-hype?
    Newshawk Crew

    About Author

    Beenthere2Hippie
    BT2H is a retired news editor and writer from the NYC area who, for health reasons, retired to a southern US state early, and where BT2H continues to write and to post drug-related news to DF.

Comments

  1. RoboCodeine7610
    Genetically engineered yeast produces opioids

    [imgr=white]https://drugs-forum.com/forum/picture.php?albumid=3673&pictureid=36085[/imgr]
    For thousands of years, people have used yeast to ferment wine, brew beer and leaven bread.

    Now researchers at Stanford have genetically engineered yeast to make painkilling medicines, a breakthrough that heralds a faster and potentially less expensive way to produce many different types of plant-based medicines.

    Writing today in Science, the Stanford engineers describe how they reprogrammed the genetic machinery of baker's yeast so that these fast-growing cells could convert sugar into hydrocodone in just three to five days.

    Hydrocodone and its chemical relatives such as morphine and oxycodone are opioids, members of a family of painkilling drugs sourced from the opium poppy. It can take more than a year to produce a batch of medicine, starting from the farms in Australia, Europe and elsewhere that are licensed to grow opium poppies. Plant material must then be harvested, processed and shipped to pharmaceutical factories in the United States, where the active drug molecules are extracted and refined into medicines.

    "When we started work a decade ago, many experts thought it would be impossible to engineer yeast to replace the entire farm-to-factory process," said senior author Christina Smolke, an associate professor of bioengineering at Stanford.

    Now, though the output is small -- it would take 4,400 gallons of bioengineered yeast to produce a single dose of pain relief -- the experiment proves that bioengineered yeast can make complex plant-based medicines.

    "This is only the beginning," Smolke said. "The techniques we developed and demonstrate for opioid pain relievers can be adapted to produce many plant-derived compounds to fight cancers, infectious diseases and chronic conditions such as high blood pressure and arthritis."

    From plant to test tubes

    Many medicines are derived from plants, which our ancestors chewed or brewed into teas, or later refined into pills using chemical processes to extract and concentrate their active ingredients. Smolke's team is modernizing the process by inserting precisely engineered snippets of DNA into cells, such as yeast, to reprogram the cells into custom chemical assembly lines to produce medicinal compounds.

    An important predecessor to the Stanford work has been the use of genetically engineered yeast to produce the anti-malarial drug artemisinin. Traditionally artemisinin has been sourced from the sweet wormwood tree in similar fashion to how opiates are refined from poppy. Over the last decade, as yeast-based artemisinin production has become possible, about one third of the world's supply has shifted to bioreactors.

    The artemisinin experiments proved that yeast biosynthesis was possible, but involved adding only six genes. The Stanford team had to engineer 23 genes into yeast to create their cellular assembly line for hydrocodone.

    "This is the most complicated chemical synthesis ever engineered in yeast," Smolke said.

    Her team found and fine-tuned snippets of DNA from other plants, bacteria and even rats. These genes equipped the yeast to produce all the enzymes necessary for the cells to convert sugar into hydrocodone, a compound that deactivates pain receptors in the brain.

    "Enzymes make and break molecules," said Stephanie Galanie, a PhD student in chemistry and a member of Smolke's team. "They're the action heroes of biology."

    To get the yeast assembly line going, the Stanford team had to fill in a missing link in the basic science of plant-based medicines.

    Many plants, including opium poppies, produce (S)-reticuline, a molecule that is a precursor to active ingredients with medicinal properties. In the opium poppy, (S)-reticuline is naturally reconfigured into a variant called (R)-reticuline, a molecule that starts the plant down a path toward the production of molecules that can relieve pain.

    Smolke's team and two other labs recently independently discovered which enzyme reconfigures reticuline, but even after the Stanford bioengineers added this enzyme into their microbial factory, the yeast didn't create enough of the opioid compound. So they genetically tweaked the next enzyme in the process to boost production. Down the line they went, adding enzymes, including six from rats, in order to craft a molecule that emerged ready to plug pain receptors in the brain.

    Engineered with a purpose

    In their Science paper, the Stanford authors acknowledged that a new process to make opioid painkillers could increase concerns about the potential for opioid abuse.

    "We want there to be an open deliberative process to bring researchers and policymakers together," Smolke said. "We need options to help ensure that the bio-based production of medicinal compounds is developed in the most responsible way."

    Smolke said that in the United States, where opioid medicines are already widely available, the focus is on potential misuse. But the World Health Organization estimates that 5.5 billion people have little or no access to pain medications.

    "Biotech production could lower costs and, with proper controls against abuse, allow bioreactors to be located where they are needed," she said.

    In addition to bioengineering yeast to convert sugar into hydrocodone, the Stanford team developed a second strain that can process sugar into thebaine, a precursor to other opioid compounds. Bio-produced thebaine would still need to be refined through sophisticated processes in pharmaceutical factories, but it would eliminate the time delay of growing poppies.

    "The molecules we produced and the techniques we developed show that it is possible to make important medicines from scratch using only yeast," she said. "If responsibly developed, we can make and fairly provide medicines to all who need."

    Stanford School of Engineering.
    ScienceDaily, 13 August 2015.
    http://www.sciencedaily.com/releases/2015/08/150813142535.htm
  2. RoboCodeine7610
    Re: Genetically engineered yeast produces opioids

    This technique seems to be advancing at an astonishing rate. I wouldn't be surprised if we had yeast-produced opiates on the shelves within 5 years.

    Robo
  3. TheBigBadWolf
    Re: Genetically engineered yeast produces opioids

    And to get the opium poppy farmers out of the business is only a small fraction of what will happen - I hear pharma say - well they can farm turnips or sugar cane instead, we need sugar to get our yeast working.

    This is the beginning of a further step in the war against drugs - whether these developpers know it or not - when the opium poppy goes extinct there's no more Poppy seed tea...

    Just saying

    BBW
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