Sciencemadness Discussion Board

GMO yeast produces opiates: challenges and opportunities

mayko - 18-5-2015 at 17:00


"Genetically Modified Yeast Will Make It Possible to Home-Brew Opiates"
http://www.wired.com/2015/05/genetically-modified-yeast-will-make-possible-home-brew-opiates/
Quote:

YEAST HAS LONG been a friend to human substance abusers. These masterful microbes, among the first fungi domesticated by humans, can take simple sugar from any number of sources and, like magic, ferment it into ethanol. Soon, though, yeast could be used to generate other, more illicit substances, bringing us one step closer to the possibility of homebrewed smack.

A paper published today in Nature Chemical Biology details a novel process for replicating poppy’s opiate-producing chemical pathways by genetically modifying good ol’ Saccharomyces cerevisiae. That technology could lay the foundation for low-cost drug discovery, potentially producing anti-cancer therapeutics, antibiotics, and other narcotics. The only hitch: With the right opioid-producing yeast strains, it would also be easier to create morphine, heroin and other drugs at home—no Walter White-level smarts required. Just call it Breaking Bread. No, wait, Brewing Bad.

“Right now, you would need a background in synthetic biology and genetics to overcome the challenges to produce the right kind of yeast,” says John Dueber, a bioengineer at UC Berkeley and lead author on the study. “It is not an imminent threat. But if a strain made for licit purposes got out, then all that would be required is knowledge of brewing beer to ferment it into morphine.”

byko3y - 18-5-2015 at 17:51

Fun to read, but I want to remind you that still scientists failed to significantly improve biosynthesis of the morphine alkaloids in poppies more, than a regular selection did.
So just like in the case with ergot, we will have 1 g of morphine from few kilos of sugar.

[Edited on 19-5-2015 by byko3y]

Bert - 18-5-2015 at 18:06

A few kilos of sugar. For a gram of morphine.

I can hear someone saying "Your proposal is acceptable"

j_sum1 - 18-5-2015 at 18:22

Agreed Bert. Sugar is not that expensive. One gram of morphine is a significant amount. There is a potential problem on the horizon here. I would guess that the pharmaceutical companies that develop this process will be pretty tight on security to protect their corner of the market and prevent the modified strains from escaping. That is not to say that some unscrupulous person might not at some stage let the horse out of the barn.

I think one of the things that buys us time in this situation is the dilution. Any illicit process to produce drugs via this route is likely to be voluminous and therefore difficult to disguise. There is also the non-trivial task of concentrating the product. Not saying it couldn't be done. Just that it is a hurdle that would need to be overcome.

macckone - 18-5-2015 at 20:17

An acceptable yield is probably 1%. That means a 55 gal drum would yield about 2 kg.
Not sure what you would feed the microbes but guessing it is more than sugar.
The solution is probably going to be 90% water so you would have to extract a 10% mixture
after boiling it down. Instead of selling drugs, dealers will be selling yeast, nutrients and
instructions.

turd - 19-5-2015 at 00:00

Quote: Originally posted by j_sum1  
There is a potential problem on the horizon here.

Not really. There are countries where (quite potent) opium poppies are/were semi-legally available (officially for ornamental purposes) and consumed in the form of poppy tea. Neither did these countries have higher opiate consumption than comparable countries, nor were there notable attempts to refine opiates from these poppies. Compared to imported heroin and diverted pharmaceutical opiates it's simply not worth it.

So the only thing that may happen is that people brew their own opiate containing concoctions. With the exception of the local mafia and warlords in opium growing countries, who would have a problem with that?

phlogiston - 19-5-2015 at 03:01

It would be easier to hide a few barrels of fermenting yeast than a field of poppies.
Its probably not a huge problem though.

Biosynthesis of alkaloids by microorganisms has been done before, and it has not been a problem so far.

http://www.yeastgenome.org/yeast-as-a-painkiller-factory
http://www.nature.com/nchembio/journal/v10/n10/abs/nchembio....
http://www.nature.com/ncomms/2014/140211/ncomms4283/abs/ncom...


[Edited on 19-5-2015 by phlogiston]

macckone - 26-5-2015 at 09:45

This will be a problem in the future. It isn't yet because you have to feed the yeast chemicals that aren't readily available. But they are working on yeasts that make these compounds from basic nutrients which is what spawned this thread. Plus the special yeasts have been kept locked up.

also on poppy cultivation. Even in the us some poppy varieties are legal. But only opium poppies produce substantial opium and they are not.

jock88 - 26-5-2015 at 10:10


Even with proper opium poppies you need proper weather. With the yeast Alaska will do grand

unionised - 26-5-2015 at 10:46

Opium poppies are perfectly legal in the UK and I don't know of any ban in the US. Is there one?
Also, they grow just fine here. My Grandmother used to grow them.

[Edited on 26-5-15 by unionised]

The Volatile Chemist - 26-5-2015 at 11:54

Genetically modified yeasts are my favorite branch of biotech. So useful. Anyone own/make any? Carolina Bio. sells a kit for adding the GFP gene to bacterium, the kit comes with E. Coli but it states it will work with yeasts too. I don't know much about that kind of stuff though.

jock88 - 26-5-2015 at 13:08


So you don't need great weather for a good yield?

The wild poppies that grow in disturbed soil (UK and France etc) are highish in opiates. These are the same poppies that grew in abundance on WW1 battle sights and are worn in commeration of WW1.

I know of a case where a person was told to 'do something about them' by the law when they grew in abundance on a building sight.
You can make a tea from them that will blow your head off/put you to sleep.

blogfast25 - 26-5-2015 at 15:57

Quote: Originally posted by jock88  


I know of a case where a person was told to 'do something about them' by the law when they grew in abundance on a building sight.
You can make a tea from them that will blow your head off/put you to sleep.


Evidence please? :)

phlogiston - 27-5-2015 at 00:13

Quote: Originally posted by The Volatile Chemist  
Genetically modified yeasts are my favorite branch of biotech. So useful. Anyone own/make any?


Yes, I used S. cerevisiae extensively to study fatty acid metabolism. Made all kinds of mutant and transgene yeast strains. Also P. pastoris a few times. But in an professional setting, not as an amateur scientists. I believe it would also not be legal where I live. There is a national register that keeps trakc of who works with what GMO's. There are laws for how to handle them and labs are sometimes inspected.

The Volatile Chemist - 31-5-2015 at 15:01

Quote: Originally posted by phlogiston  
Quote: Originally posted by The Volatile Chemist  
Genetically modified yeasts are my favorite branch of biotech. So useful. Anyone own/make any?


Yes, I used S. cerevisiae extensively to study fatty acid metabolism. Made all kinds of mutant and transgene yeast strains. Also P. pastoris a few times. But in an professional setting, not as an amateur scientists. I believe it would also not be legal where I live. There is a national register that keeps trakc of who works with what GMO's. There are laws for how to handle them and labs are sometimes inspected.

Really? That sucks. I was really kind of hoping to sell them later in life. Where do you live, the US?

phlogiston - 1-6-2015 at 06:08

No, the Netherlands.
Depending on what you want to do exactly, there are sometimes ways to get around it, i.e. to obtain a strain with a desired mutation that you did not introduce via 'genetic modification'.

This is the kind of thing you would do if you really wanted to use a certain mutant for, say, brewing beer but don't want to have to label your beer as 'GMO'.

It is much more work though.

The Volatile Chemist - 4-6-2015 at 12:06

I'm talking about selling bacterium containing things like GFP to the public. I suppose that's restricted? Carolina Bio. sells $75 kits, but you have to modify the organism yourself, so I guess they're not selling GMOs.

superamoeba - 5-4-2021 at 03:52

Quote: Originally posted by unionised  
Opium poppies are perfectly legal in the UK and I don't know of any ban in the US. Is there one?
Also, they grow just fine here. My Grandmother used to grow them.

[Edited on 26-5-15 by unionised]


In the US, the only part of the P. somniferum plant that is LEGAL to possess are the seeds because they contain zero active alkaloids. It is illegal to grow the plants at all, however, I do see people who get away with doing it in their front yards every year. So, either it is mildly tolerated or most police don't really know what they look like.

[Edited on 5-4-2021 by superamoeba]

Fyndium - 5-4-2021 at 05:20

The bad people interested in this would be very interested in brew that turns 2kg of sugar into 1g of morphine. 200L barrel could possibly then make 50-100g of it, if it's as fast as brewing, it takes less than one week including processing it. The price per gram is so high that it would still warrant thousands of % of profit. The effective kg price would be less than 1000$. It must be noted that while something is very cheap in parts of the world it is produced, it can cost thousand times more in other parts, making even very rudimentary production methods highly lucrative, because logistics effectively make the risk-profit ratio too low to transport it. Even more, if there is no organization to share the profits, but it's run by few, even very small scale with little capital costs can make the profit ratio enormous. The classic scheme involves multiple steps from high purity to low price going all the way down to low purity and high price.

karlos³ - 5-4-2021 at 09:13

The bad people who would be interested in this must be very stupid bad people because the cost of growing and smuggling raw opium is magnitudes lower than the price of making it with GMO yeast.

Texium - 5-4-2021 at 10:27

Quote: Originally posted by Fyndium  
The bad people interested in this would be very interested in brew that turns 2kg of sugar into 1g of morphine.
It's impossible to convert plain sugar into morphine... considering morphine contains nitrogen and sugar does not. The yeast necessarily requires a nitrogen containing feedstock that it is able to process as well. Ideally, this could be something as simple as an ammonium salt, but it may not be that easy. Yeast requires additional nutrients to thrive as well. Even using unmodified yeast to produce alcohol from sugar water is not sustainable without extra nutrients. For someone making moonshine with cheap commercial yeast, this isn't generally a concern, because you can just buy fresh yeast for each batch (and quite often, commercial yeast includes some key nutrients anyway). On the other hand, buying more expensive GMO yeast for every batch is certainly not profitable.

karlos³ - 5-4-2021 at 11:28

Quote: Originally posted by Texium (zts16)  
On the other hand, buying more expensive GMO yeast for every batch is certainly not profitable.

Not to forget, this stuff is years away from being something you could encounter on the drug producing markets.

And when it will hit them, it will be a monopoly that will tend to outcompete all the naturally made(e.g. via poppy) procedures, which it will possibly do in around 10-15 years, maybe 20.
But at this point, the world will be different anyways.

draculic acid69 - 7-4-2021 at 02:46

I remember when news about this first broke and I see that this thread is missing a vital part of the story: As soon as the scientists who did this succeeded they let law enforcement and government in on the creation for the purpose of making laws against using selling or possessing this yeast so that instead of the usual game of catch-up of the law trying to get precursors outlawed for years was avoided thus ensuring that there creation was never used outside of predetermined purposes. It was the first time this sequence of events has ever occurred.

zed - 9-4-2021 at 04:16

Piffle. Making Opioids is fairly easy. One of my associates was doing it 40 years ago.

This of course, led to his becoming a pathetic dope fiend. Which was sad.

The original post was six years ago. I'm not sure of dates, but CRISPR has come into common use now.

Meaning... genetically engineered organisms, are easier to produce now.

As for Opium Poppies.... They are not uncommon in the USA.

The related Papavar Bracteatum is very common, not illegal to grow, and has a high Thebaine content.

Poisonous as is, but easily converted to Oxycodone, Numorphan, or the dreaded M99.

Now, Lysergic Acid derivatives; THERE bioengineering has potential. Producing Ergot alkaloids, isn't easy. And, existing organisms have resisted manipulation.



[Edited on 9-4-2021 by zed]

karlos³ - 9-4-2021 at 06:43

What, we already have lysergic acid producing yeast.
Thats not new either.

zed - 9-4-2021 at 22:13

You know something about Lysergic acid producing yeast? Stop holding out!

Tell us about it! Give us a link.

[Edited on 10-4-2021 by zed]

IrishJeremy - 16-4-2021 at 12:11

Quote: Originally posted by superamoeba  
Quote: Originally posted by unionised  
Opium poppies are perfectly legal in the UK and I don't know of any ban in the US. Is there one?
Also, they grow just fine here. My Grandmother used to grow them.

[Edited on 26-5-15 by unionised]


In the US, the only part of the P. somniferum plant that is LEGAL to possess are the seeds because they contain zero active alkaloids. It is illegal to grow the plants at all, however, I do see people who get away with doing it in their front yards every year. So, either it is mildly tolerated or most police don't really know what they look like.

[Edited on 5-4-2021 by superamoeba]




Papaver Somniferum are not illegal to grow in the US, there are companies that sell the dried pods for "ornamental" reasons such as flower arranging, but it's pretty obvious what they are really being bought for. What's illegal is growing them with the intent to extract the active drugs, and actually extracting them. You can grow them in your garden if you want.

Fyndium - 17-4-2021 at 00:21

Quote: Originally posted by karlos³  
The bad people who would be interested in this must be very stupid bad people because the cost of growing and smuggling raw opium is magnitudes lower than the price of making it with GMO yeast.


Don't you see a pattern here? Some dope costs 1000$/kg in Asia, and it commands a million in the other parts of the world, yet one would need to travel through a lot, and know contacts and fear of getting robbed or incarcerated for life, as Asians tend to treat narco guys pretty unfriendly. Smuggling needs organizations, and organizations eat profits for living.
Quote: Originally posted by Texium (zts16)  
It's impossible to convert plain sugar into morphine... considering morphine contains nitrogen and sugar does not. The yeast necessarily requires a nitrogen containing feedstock that it is able to process as well. Ideally, this could be something as simple as an ammonium salt, but it may not be that easy. Yeast requires additional nutrients to thrive as well. Even using unmodified yeast to produce alcohol from sugar water is not sustainable without extra nutrients. For someone making moonshine with cheap commercial yeast, this isn't generally a concern, because you can just buy fresh yeast for each batch (and quite often, commercial yeast includes some key nutrients anyway). On the other hand, buying more expensive GMO yeast for every batch is certainly not profitable.


Yeast is grown in aerobic environment, and alcohol in anaerobic. One turns booze batch into yeast batch by aerating it. Yeast is grown by the ton this way industrially. I've done both, and yes, I know about nutrients, and have taken that also in consideration. Nutrients are sold in bags in every brewing store anyway, if one doesn't bother using ordinary supply. Yeast can even cannibalize itself if necessary.
Quote: Originally posted by draculic acid69  
I remember when news about this first broke and I see that this thread is missing a vital part of the story: As soon as the scientists who did this succeeded they let law enforcement and government in on the creation for the purpose of making laws against using selling or possessing this yeast so that instead of the usual game of catch-up of the law trying to get precursors outlawed for years was avoided thus ensuring that there creation was never used outside of predetermined purposes. It was the first time this sequence of events has ever occurred.


If it's really kept in some highly developed country in specific research purposes only, it might stay off for a while, but likely Chinese will eventually develop one because they can either profit from it by using it themselves or selling it to others, and once it's out, it ain't getting back in. Something worth money with known directions tend to be dug upon, and only good way to keep something off the radar is to keep it's whole existence as a secret. NSA has this scheme: they file secret patents, and if someone files a similar enough, they will come public with it and reserve a 10-year proprietary patent for it at once.

Texium - 17-4-2021 at 06:59

Quote: Originally posted by Fyndium  
Quote: Originally posted by Texium (zts16)  
It's impossible to convert plain sugar into morphine... considering morphine contains nitrogen and sugar does not. The yeast necessarily requires a nitrogen containing feedstock that it is able to process as well. Ideally, this could be something as simple as an ammonium salt, but it may not be that easy. Yeast requires additional nutrients to thrive as well. Even using unmodified yeast to produce alcohol from sugar water is not sustainable without extra nutrients. For someone making moonshine with cheap commercial yeast, this isn't generally a concern, because you can just buy fresh yeast for each batch (and quite often, commercial yeast includes some key nutrients anyway). On the other hand, buying more expensive GMO yeast for every batch is certainly not profitable.


Yeast is grown in aerobic environment, and alcohol in anaerobic. One turns booze batch into yeast batch by aerating it. Yeast is grown by the ton this way industrially. I've done both, and yes, I know about nutrients, and have taken that also in consideration. Nutrients are sold in bags in every brewing store anyway, if one doesn't bother using ordinary supply. Yeast can even cannibalize itself if necessary.
Yes, I’m well aware of how growing yeast works. I grew up around breweries. My point was that your initial assertion of “converting 2kg of sugar into 1g of morphine” is oversimplified and unrealistic. You still need a nitrogen-containing feedstock, and unless they can incorporate an ammonium salt or urea, that’s certainly going to be more expensive than the sugar. Still profitable? Sure, if everything else is done right. But not quite as extreme.

Regardless of whether this becomes available to “bad people,” it’ll only be the more sophisticated ones who are able to use it successfully. Reproducing a strain of yeast for many generations while retaining the same traits is not trivial. You have to keep it sealed off from contamination by any wild yeasts (which are everywhere), and aerate it with sterile air, or else you’ll end up finding that your special yeast isn’t so special anymore.

karlos³ - 17-4-2021 at 10:16

Quote: Originally posted by Texium (zts16)  

Regardless of whether this becomes available to “bad people,” it’ll only be the more sophisticated ones who are able to use it successfully. Reproducing a strain of yeast for many generations while retaining the same traits is not trivial.

Yeah I'll hope to obtain such a strain at some point in the future :)
I figure it will be easier than obtaining a good ergot strain, and that was definitely not complicated.

But I'm even more after the THC yeast :D
The lysergic acid yeast, meh...

Fyndium - 17-4-2021 at 16:27

Shouldn't one just anyway keep a separate cultivation setup for the desired yeast and only pick more when needed with clean/sterile equipment? Yeast can also be dried, frozen, etc.

I'm not sure how yeasts are developed. Are they just cultivating countless batches with desired conditions and keep looking if any strains adapt forward desired behavior, and once any improvement is noticed, breeding that strain further so that only the best survive in the more and more harsh environment, until a limit comes up? Like oil and plastic eating yeasts, and so on.

draculic acid69 - 19-4-2021 at 20:02

Anyone who got there hands on it would obviously know how to treat it and keep it going. No one is Gunna get there hands on this op8 producing yeast and then go "so I
just Chuck it in a beer fermenter right" . Anyone who got there hands on it is going to know what there doing and will understand the required sterile rooms, equipment and practices needed. This isn't something a janitor could steal and then sell down at the pub.

Fyndium - 22-4-2021 at 00:09

I've seen various instances when people have gotten their hands on something they have no clue how to handle.

I've been told that I'm a professional and I know what I'm doing just because I have a business registered. Well, not quite. I just know how to register a business.

The difference is, if someone could get something, but could they turn it into something useful. Quite a lot of stuff is useless for most of the people because they have no skillset for utilizing them. A simple chemical synthesis is something that more than 50% would fail even with decent instructions.

symboom - 30-4-2021 at 17:56

https://www.reddit.com/r/DrugNerds/comments/my6q19/complete_...

Without genetic engineering, Biosynthesis only tends to be helpful if you can take advantage of the activity of an enzyme that is already present. Take for example the activity of producing l-PAC from benzaldehyde in yeast. Some others hypothesize that safrole can be produced from Vanillin if fed to some certian species of soil bacteria.


You would need equipment to make a stable cell line expressing the necessary genes and subsequent culture of the yeast. Then you'd need equipment for the scale-up from initial cell line creation to a volume big enough to produce an appreciable amount (so a large bioreactor, or lots of incubators with space for flasks). Then you would need a purification process to extract the morphine from the yeast media and remove everything else. I'm not going to cover that here but it's a whole separate endeavor from MAKING the morphine.

To get past even the first step, you would need:

Space to culture the yeast. An incubator, specifically a 37 DegC one that keeps a certain % of CO2 in the incubator air.Here's an article on how to DIY one for $350. Here's a manufactured one for $1500 on ebay.
A hood to perform sterile work in, so your yeast culture does not become contaminated. Here's one for $1500 on ebay and here's a new HEPA filter for it. You'd need some bleach to decontaminate it when you started, and ethanol to clean it before every use.
General lab equipment (pipettes, centrifuge...) Here's some pipettes. This centrifuge might work. You'd also need some consumables.
Big one: Cell culture media. The yeast needs to grow in a specific solution. You dissolve this stuff in water but then need to sterilize it... which leads to next item.
Autoclave. You need to be able sterilize the flasks you culture with, as well as anything that will directly touch the yeast culture (glass pipettes when replacing culture media, among other things.)Here's a cheap one.
So to total up this shitty list... 1500 + 1500 + 900 + 500 + 160 + 100 = about $5000. Then add in all the money you'd spend on tubes, media, and culture flasks and all the other things I didn't mention.

_oEeMaETXqX-t_WwLQK-mQonu9oQpQK3mM3xscoENiE.jpg - 51kB

Fyndium - 1-5-2021 at 03:56

Equipping a decent small lab easily costs $5k. And the guys that would do that morphine thing, will invest 10 times that to get all the stuff, because the expected ROI is so high. Industry gets that 100-fold, because they can provide steady income for years to come. Not to mention that there is evidence that state actors like NK are doing that stuff, so the cost is definitely not an issue, although they might not actually pay to their workers, but instead make to choose between medal of the hero of labor and an isotope of lead.

So, while it's not in the reach of shake-and-bakes, it's definitely not a cost issue for the ones who might be interested. People come from various conditions, and I know people who can merely afford food, the ones ordering $30 GPU:s from Ali, and then I've got friends who tune cars and they don't hesitate another second to throw $30k into some project. I place myself on the middle, I suppose, as using few thousand per year into a hobby that I like very much is a good investment in my view.