• N&PD Moderators: Skorpio | thegreenhand

Transgenic yeast used to 'brew' lsd

Interesting.

I don't know enough about biology and genetic modification to really make much out of that, but I've always thought that as we are about to undergo a biotech revolution to rival our current computer tech one, manufactoring drugs in this way will soon become both cheap and easy.

I can imagine that producing shitloads of LSD will become as easy as growing shrooms or making your own beer.
 
Well, psychopharmacology is the cutting edge of nano/neuro-technology.

There's a mckenna quote in his talk Psychedelics in the Age of Intelligent Machines where he says: "computers and drugs are function specific arrangements of matter...the only difference is one is too big to swallow and our best people are working on that." Regardless about what you think about his ideas on hyperspace and 2012, Mckenna is totally underrated as a social commentator on emerging immersive technologies.

The whole idea of transgenic yeast is pretty crazy though and completely feasable. Basically it's the same idea as Genetically Modified Foods, or engineering pesticide resistant crops.

look at the pharmaceutical industry though, the biotech revolution is already here.
 
cognosis said:
look at the pharmaceutical industry though, the biotech revolution is already here.

True, but it's only just starting. Within the next 10 years or so we'll see it get so cheap and easy that projects lacking large scale (legally) profitable uses, like producing LSD from yeast, will actually be practical.

Kind of like with computers how at first there were a few big expensive mainframes owned by the large companies and now everyone has one.
 
MrM said:
True, but it's only just starting. Within the next 10 years or so we'll see it get so cheap and easy that projects lacking large scale (legally) profitable uses, like producing LSD from yeast, will actually be practical.

=D =D =D you should check this out too.
 
Looks cool, but mostly just makes me wish i knew more about chemistry.
 
yeah me too. right now i'm focusing on biology so later on when I take chem courses it will just be the math I have to figure out. with Bio its a lot more of a pain in the ass to learn/memorize everything IMO. right now I'm taking some courses on genetics and that's how I found the transgene yeast article..If you noticed, it's written by Dennis Mckenna but apparently there's some controversy about that aswell.


The syn gen program is supposed to make synthesis of organic compounds easier by showing you the quickest steps and precusors you'd need. Also I heard somewhere you can set it to create computer generated analogs of a known psychoactive (ie. Savinorum A). Crazy stuff.
 
Very interesting study indeed, I for one am certainly looking to see the progress in this field (bioenzymatic synthesis of psychedelics). Hopefully one day these bacteria will replace the chemicals altogether and everyone will be only required to order these bacteria and able to brew and extract their own chemicals.
 
I think it's totally possible, you just need to get someone to scrap together 10-15k for a lab to create the transgenic yeast and then you can distribute it however you see fit.
 
Of course you'll also need someone very knowledgeable about genetic engineering in both theory and practice.
 
The main problem I see with this, at least for LSD, is that LSD is not a naturally occurring substance. Therefore there are no known enzymatic paths to it. Ergotamine or LSA I could easily see being produced, but not LSD.
 
^ To get to LSD from lysergic acid amide, you only need to add two ethyl groups. Now I am not an expert, but I am fairly certain natural enzymes for that process exist in a number of organisms.
 
This does actually break forum rules- no synthesis threads. Interesting however...

Re-opening and moving to ADD as per request of F&B. Enjoy.
 
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The DEA will create List I and List II microorganisms of which saccharomyces uvarum will be List I and what will Anheuser-Busch do then?

Stoopid acid-heads ruining it for the beer guzzlers! :X

:D
 
Does anyone know where this originally came from? Was it published in anywhere?
 
I would think organisms would have more cellular machinery devoted to removing ethyl and other small alkyl groups from small molecules as opposed to putting them on, just due to the havoc these groups can wreak when on a lot of biologically relevant small molecules like nucleotides.

Still, even if alkylating enzymes are prevalent, the chances that LSA, or even mono-alkylated LSA would act as a substrate are, I would think, be pretty grim.

Nonetheless, this method would still probably work pretty damn well for the naturally occurring tryptamines and phenethylamines.
 
It's not too troublesome to modify a methyl transferase to an ethyl transferase. It also would not be especially difficult to modify the aminating enzyme to use diethylamine instead of ammonia. A little directed evolution here, site specific mutagenesis there, bam, its there.
The problem right now is that the full operon/genome of the lysergic acid producing species is not known. There are a few enzymes know in the pathway, but the full synthesis is large, perhaps 15 steps from tryptophan, and these would all have to be imported and properly regulated into another organism to make it feasible, which is not as easy as it seems. Precursor production must be stepped up, along with upregulation of all genes involved, native or transgenic. And you have to deal with toxicity issues. I don't have all my synthetic pathway papers on me now or I could be more specific.
Keasling & co got the artemisinin pathway into yeast, which was a LOT of work to optimize, and they finished about 3 synthetic steps away from the final product(artemisinic acid), I'm not sure why...
The project took around 3 years if I'm not mistaken, with over 30 million in funding and a slew of ultra talented grad students and post-docs. Joe Hippie would have a hard time pulling this off.
Why not just culture claviceps strains? Or ipomoea species?
Morphine would be a fun one to import, but again, it's so much easier to culture poppies. There really isn't a drug that is worth producing via submerged culture that can't be more economically synthesized or grown in it's native state.
What I would like to do, is take some of the final tailoring enzymes, and evolve them to make combinatorial libraries of drugs in vivo. Imagine, each plant, or bacterium, or yeast, producing a slightly modified drug of interest. You could recreate all of PIHKAL in one greenhouse or a few dozen culture tubes.
 
Recept said:
^ To get to LSD from lysergic acid amide, you only need to add two ethyl groups. Now I am not an expert, but I am fairly certain natural enzymes for that process exist in a number of organisms.

You are most certainly correct. It is like a game of mix and match.

Who wants to engineer shrooms with custom mixes of tryptamines built in? I do!
 
kidamnesiac said:
It's not too troublesome to modify a methyl transferase to an ethyl transferase. It also would not be especially difficult to modify the aminating enzyme to use diethylamine instead of ammonia. A little directed evolution here, site specific mutagenesis there, bam, its there.
The problem right now is that the full operon/genome of the lysergic acid producing species is not known. There are a few enzymes know in the pathway, but the full synthesis is large, perhaps 15 steps from tryptophan, and these would all have to be imported and properly regulated into another organism to make it feasible, which is not as easy as it seems. Precursor production must be stepped up, along with upregulation of all genes involved, native or transgenic. And you have to deal with toxicity issues. I don't have all my synthetic pathway papers on me now or I could be more specific.
Keasling & co got the artemisinin pathway into yeast, which was a LOT of work to optimize, and they finished about 3 synthetic steps away from the final product(artemisinic acid), I'm not sure why...
The project took around 3 years if I'm not mistaken, with over 30 million in funding and a slew of ultra talented grad students and post-docs. Joe Hippie would have a hard time pulling this off.
Why not just culture claviceps strains? Or ipomoea species?
Morphine would be a fun one to import, but again, it's so much easier to culture poppies. There really isn't a drug that is worth producing via submerged culture that can't be more economically synthesized or grown in it's native state.
What I would like to do, is take some of the final tailoring enzymes, and evolve them to make combinatorial libraries of drugs in vivo. Imagine, each plant, or bacterium, or yeast, producing a slightly modified drug of interest. You could recreate all of PIHKAL in one greenhouse or a few dozen culture tubes.

Firstly, what class should I take for this stuff?

Secondly, would I be right in assuming this would be much easier with compounds such as a,O-DMS?
 
It also would not be especially difficult to modify the aminating enzyme to use diethylamine instead of ammonia. A little directed evolution here, site specific mutagenesis there, bam, its there.

Or skew the substrate composition to favour alkylated amines over ammonia. That how they did it with submerged batch culture of C. paspali
 
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