Metabolic conversion of trytophan to tryptamine

[batmanboner]

First, off, mods, feel free to delete this post if it's too speculative.

We all know tryptophan is structurally similar to tryptamine, and DMT is of course a derivative of tryptamine. I don't believe in the crack pot theories about there being an existent metabolic pathway from this amino acid to DMT in humans, however, there is obviously some way of synthesis of tryptamine in the human brain, as trace amounts of tryptamine are present in the mammalian brain.

So my question is, would it be possible to transform the genes of a couple of enzymes that produce the tryptamine in mammals, and then some enzyme that methylates the amino group of trpytamine, into the plasmid of a bacterium? It seems like it's something that's been done with more complex molecules, such as insulin and HGH in bacteria. This process seems like it could be done by almost anyone -- hell, I did a similar kind of transformation in my high school bio class.

Does this seem plausible?

 

[sekio]

As the MythBusters say, "plausible but not very possible".

Mother Nature has already kind of solved your problem for making DMT easily. Don't forget DMT is produced in e.g. Acacia spp. (plants used in ayahuasca) in quite good yields - it would be easy enough to express the requisite enzymes (tryptophan decarboxylase, tryptamine N-methyltransferases) in e.g. E. coli, or even simply have them expressed as extracellular protiens. Then you could immobilise them on a polymer matrix and "wash" tryptophan broth (with some other nutrients) over the enzymes and have them make e.g. DMT or psilocin. (or just have E.coli that make ayahuasca out of sugar water and autolysed yeast extract)

And speaking of psilocin, as far as I know the fungal synthetic pathway to 4-HO-DMT could also be easily "knocked out" to produce "plain" DMT. In theory, anyway. I believe people have isolated the enzymes that 'shrooms use to make tryptamines/phopshates.

Presence of tryptamine in the mamalian brain is not because it is actively synthesized, it is an artifact of enzymes being non-selective (normally tryptophan is hydroxylated before being decarboxylated). I wouldn't be using human tryptamine N-methyltransferase !

 

[batmanboner]

That makes sense about using the more adapted DMT producing plants' enzymes. Do you think this is just too costly and inefficient to ever be used? It seems like it would solve a lot of DMT's purity problems, especially in terms of accidentally extracting other alkaloids, and pretty much you only have to do it once to get an infinite supply.

 

[sekio]

Do you think this is just too costly and inefficient to ever be used?

The purification process is already such that it's cheapest to just greenhouse-grow acacia and extract from root bark. The benefit with plants is that they essentially grow from nothing (rain for hydrogen/oxygen, nitrogen fixed into the soils via bacteria, carbon from carbon dioxide). whereas microbes would need to be fed on nutrient broth.

DMT of consistently high purity can usually be had after simple freeze crystallization from alkaloid "mother liquors". and some varieties of plant only produce DMT in appreciable quantities anyway.

 

[JimRaynor]

Hmm, but hallucinogen-producing-bacteria could be really cool stuff. Does any known bacteria produce MAOI's?

Just think about putting DMT-producing bacteria and MAOI-producing bacteria into some yoghurt of sorts. Then when you drink it the bacteria would colonize the digestive tract and transform ANYTHING you eat into DMT and send you on a trip. :D Everything edible would become a hallucinogenic drug, until you take the right antibiotics.

 

[sekio]

Depends on what you mean by MAOI. Plants produce all sorts of compounds that could be MAOIs if concentrated enough. (the flavonoids spring to mind) It wouldn't be a stretch to find an organism that made e.g. phenethyl hydrazine as a metabolite, I don't think.

I would imagine tryptamine-producing bacteria would be pretty immunoreactive - at the very least they would cause severe gastric issues

 

[Dmytry]

it wouldnt be too hard for a biochem engineer i would think. i mean, today, bacteria make the worlds supply of insulin. its just genetic engineering, but it wouldnt be done unless dmt became a pharmaceutical, or you knew someone with access to that kind of lab. and even still, dmt is a relatively simple molecule, it makes more sense to just make it in a flask from indole

 

[batmanboner]

At least in a future where DMT producing plants are banned, this may at least be a more clandestine method of production.

 

[NielsBohr]

http://www.ncbi.nlm.nih.gov/pubmed/21080162
Serotonin is produced by dual expression of tryptophan decarboxylase and tryptamine 5-hydroxylase in coli to accumulate up to 24 mg/L in the culture medium. Functional expression of T5H involved N-terminal sequence optimization and fusion protein technology (GST).

http://www.ncbi.nlm.nih.gov/pubmed/4960870
Tryptamine is produced by Bacillus cereus growing in tryptophan containing broth

http://www.ncbi.nlm.nih.gov/pubmed/24508833
DMT was identified in the supernatant of cultured human melanoma cell line SK-Mel-147

http://www.ncbi.nlm.nih.gov/pubmed/23881860
LC/MS/MS analysis of the endogenous dimethyltryptamine hallucinogens, their precursors, and major metabolites in rat pineal gland microdialysate

Read literature, then start speculations.

 

[sekio]

Try not to revive threads from 2012.