cognosis
Bluelighter
- Joined
- May 12, 2006
- Messages
- 230
N&PD Moderators: Skorpio | thegreenhand
cognosis said:look at the pharmaceutical industry though, the biotech revolution is already here.
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.
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.
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.
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.