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Yeast That Make Morphine: Cool Biotech

Migrated topic.

Nathanial.Dread

Esteemed member
I believe on The Nexus we've talked about the feasibility of putting the biosynthetic pathway for DMT into yeast (it's a much simpler pathway than morphine from glucose, so long as you can feed the yeast tryptophan).


Home-brewed heroin could become a reality, scientists have warned, following the creation of yeast strains designed to convert sugar into opiates.

The advance marks the first time that scientists have artificially reproduced the entire chemical pathway that takes place in poppy plants to produce morphine in the wild.

Scientists warned that the findings could pave the way for opium poppy farms being replaced by local morphine “breweries” and called for urgent regulation of the technology. In theory, opium brewing would be no more difficult to master than DIY beer kits, raising the possibility of people setting up Breaking Bad-style drug laboratories in their own homes.

Tania Bubela, a public health professor at the university of Alberta and co-author of a commentary on the research in the journal Nature, said: “In principle, anyone with access to the yeast strain and basic skills in fermentation could grow morphine-producing yeast using a home-brew kit for beer making.”

The team behind the advance have stopped one step short of linking together the entire chemical chain within a single easy-to-brew yeast strain, and announced a self-imposed moratorium on the work to allow law enforcement agencies and regulators time to catch up.

“We’re certainly not aiming for the illicit drugs market, that’s for sure,” said Vincent Martin, a microbiologist at Concordia University in Québec and co-author. “We realised that we’re entering into a brave new territory here. Me and my collaborators felt that various regulatory bodies should be consulted and talked to and we should build a consensus of how to take this forward.”

The findings, published in the journal Nature Chemical Biology, mark a turning point in efforts that have been made for more than a decade to replicate in microbes the 15-step chemical pathway in the poppy plant.

Scientists had previously succeeded in reproducing the second half of the chemical pathway, but the initial conversion of glucose to a compound called reticuline had proved a sticking point. The latest study cracks this problem for the first time by inserting genes from the poppy plant, sugar beet and a soil-dwelling bacteria into yeast.

Several existing yeast strains are available that can turn reticuline into morphine, and the scientists said that combining the two halves of the process was now feasible – although they have not yet attempted this final step.

“What you really want to do from a fermentation perspective is to be able to feed the yeast glucose, which is a cheap sugar source, and have the yeast do all the chemical steps required downstream to make your target therapeutic drug,” said John Dueber, lead author and a bioengineer at the University of California, Berkeley. “With our study, all the steps have been described, and it’s now a matter of linking them together and scaling up the process. It’s not a trivial challenge, but it’s doable.”

He predicted a timeline of a “couple of years, not a decade” for the reliable production of controlled drugs by sugar-fed yeast.

Being able to synthesise opiates in the laboratory raises the possibility of engineering new therapeutic forms of the drug, designed to be less addictive, more powerful or longer lasting, for instance.

“It creates a platform for finding new chemical structures that could have a lot of potential benefits,” said Martin.

However, it also raises concerns about the yeast falling into the wrong hands. In their commentary, Bubela and colleagues at the Massachusetts Institute of Technology (MIT) call for urgent regulation of the technology warning that it could lead to an alternative system for current criminal networks, particularly in North America and Europe, where the drugs are in high demand. “Because yeast is so easy to conceal, grow and transport, criminal syndicates and law-enforcement agencies would have difficulty controlling the distribution of an opiate-producing yeast strain,” the authors write. “All told, decentralised and localised production would almost certainly reduce the cost and increase the availability of illegal opiates - substantially worsening a worldwide problem.”

Future strains of morphine-producing yeast could be designed to have unusual nutrient requirements as a biocontainment measure, Bubela suggests. Such strains should also be kept in bio-secure facilities in the future, with similar safeguards to those used by researchers working with anthrax or smallpox.

Globally, more than 16 million people use opiates illegally. The drugs come from the misuse of prescription pain medications and from illegally cultivated poppy crops in countries such as Afghanistan, Laos and Mexico.

“The time is now to think about policies to address this area of research,” said Dueber. “The field is moving surprisingly fast, and we need to be out in front so that we can mitigate the potential for abuse.”

Martin said the team had no plans to complete the chain until regulations were in place to do so safely. “If this is something that we shouldn’t do, let’s talk about it now,” he added.

Blessings
~ND
 
I'm glas you posted this. I saw an article on this in new scientist this month and was intrigued. Some of the things that were brought up were the implications to the drug trade, as well as to the way people think about drugs, if a cheap effective way to produce them effectively at home could be achieved.

Apparently, if the three groups around the globe doing this research got together tomorrow, the beginning, mid and end stage of this pricess could be put together, all 2500 opiate alkaloids could be produced with yeasts. However ironing out the kumos will take years, but still, this is a when, not an if.

So who here is working on the trypty variant of thus?

Screw grandma's heirloom sourdough, give me uncle bob's morphine bread.
 
null24 said:
I'm glas you posted this. I saw an article on this in new scientist this month and was intrigued. Some of the things that were brought up were the implications to the drug trade, as well as to the way people think about drugs, if a cheap effective way to produce them effectively at home could be achieved.

Apparently, if the three groups around the globe doing this research got together tomorrow, the beginning, mid and end stage of this pricess could be put together, all 2500 opiate alkaloids could be produced with yeasts. However ironing out the kumos will take years, but still, this is a when, not an if.

So who here is working on the trypty variant of thus?

Screw grandma's heirloom sourdough, give me uncle bob's morphine bread.
There had been (mostly hypothetical) talk here on the Nexus about making DMT or psilocybin-producing yeast.

In theory, it should be much easier than the production of morphine because, so long as you fed the yeast with a substrate of tryptophan, it's only two metabolic steps from tryptophan to DMT, which is just two enzymes.

Making psilocybin would probably be a bit trickier, but again, should be much easier than morphine, especially since I imagine that the yeast genome is much more closely related to the psilocybe fungus genome than it is to an opium poppy.

Blessings
~ND
 
Wow. This is beautiful work. When these things "escape" the lab, it will revolutionize drug culture. Instead of buying drugs, you'll buy a microorganism that can be used to produce the drug indefinitely. Where do we start? :want:

What are the limitations of this sort of thing? Could a microorganism produce LSD or, say, organic compounds for solar cells? Will we someday produce nanoelectronics this way?
 
hixidom said:
Wow. This is beautiful work. When these things "escape" the lab, it will revolutionize drug culture. Instead of buying drugs, you'll buy a microorganism that can be used to produce the drug indefinitely. Where do we start? :want:

What are the limitations of this sort of thing? Could a microorganism produce LSD or, say, organic compounds for solar cells? Will we someday produce nanoelectronics this way?
As it stands now, we can only make compounds that are made in nature already. What we do is essentially steal the machinery that makes the compound of interest from an organism that makes it naturally, and insert it into our target creature.

For the psilocybin-yeast example from above: we can take the process that makes psilocybin out of mushrooms and put it into the yeast, so that when we feed it tryptophan, the same process that happens in mushrooms happens in the yeast.
We couldn't do LSD because it doesn't appear naturally, and so the machinery to make it doesn't exist. We can't make the machines, we can just move them around. Maybe we'll be able to someday, with designer enzymes, but not now.

Blessings
~ND

(I hope that explanation made sense, I'm sick, and, in an attempt to dull the pain, very stoned :p )
 
(I hope that explanation made sense, I'm sick, and, in an attempt to dull the pain, very stoned Razz )
It made sense. Thanks for the explanation. I thought they were something like designer enzymes, or that they had bred yeast to produce more and more of a substance that yeast already produced in trace amounts.
 
I also read this article elsewhere, very intersting. My first thought was; "Well, there goes Tasmania's economy."

Now somebody find benzyme and tell him to get onto some DMT-producing yeast! :lol:
 
hixidom said:
(I hope that explanation made sense, I'm sick, and, in an attempt to dull the pain, very stoned Razz )
It made sense. Thanks for the explanation. I thought they were something like designer enzymes, or that they had bred yeast to produce more and more of a substance that yeast already produced in trace amounts.
I wish. Designer enzymes would change the world, but they're a pretty long way from reality right now. There are some pretty big hurdles to get over in the field of proteomics and biochemistry before we can even think about making them.

There has been talk of it before (you can read it here), but the conversation was long, very technical, and ultimately, fruitless.

Blessings
~ND
 
Could this be done with kombucha culture, adding tryptophan to thousands of vials of culture medium and then mixing those cultures applying different stimulus until one tested positive for psilocybin? Slowly making the environment more and more inhospitable for the culture. Kind of how we create different strains already?

I am thinking Kombucha because there is a large colony of yeasts and bacteria that adapt to different environments already.
 
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