Cannabinoids through biotechnology

Cannabinoids can easily be synthesized by other organisms. Transgenic Tobacco leaf cells produced THCA when fed CBGA. If some more extensive engineering was done; you could produce THCA or any other cannabinoid from sugar. This has already been done with yeast and Morphine.
Eliminating the plant fom the biosynthesis of these products gives one the ability to produce any canabinoid, on demand, without unwanted side reactions.
What are your thoughts?

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The pathay for morphine has yet to be completed in a single organism (for fairly obvious reasons).

The pathay for THCa has actually already been completed and found to be effective at research level (yeast will express milligram quantities in a reasonable timeframe currently).

Here’s the DOI if you haven’t seen it … 10.1016/j.jbiotec.2015.06.425 … I’ll let someone else illegally download and host it here :wink:

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As for ‘thoughts’ … I think biosynthetic chemistry IS going to be the dominant force driving chemistry soon. Why spend hours with costly reagents and scientists, when maintaining a bunch of reactors costs virtually nothing?

Even our most complex total syntheses could be improved through biosynthetic pathways. Sure, maybe the real complex synthetic chemistry might still need to be done in flasks, but the workup will almost certainly come from genetically modified cells.

I’ve already heard murmurs of a UK CBD supplier working on bringing bio-reactor CBD to the UK.

Undeniably the future of chemistry.

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Does biopulping the biomass count as biosynthetic chemistry?

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CRISPR is also about to explode and making gm yeast that produces thca could be created by an amateur at home. i know the “bio-hackerlab” in oakland is already expirementing with crispr

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i saw a patent online that claimed to hav the dna sequences used to acheive this

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Agreed that biosynthetic is the way to go for high value pharmaceuticals. The ROI on the R&D is probably there. However, pure cannabanoid isolates are only worth so much IMO - there definitely seems to be some value in the full expression of the cannabis plant. Yes, we can try to re-create what mother nature is doing in the lab with single, isolated chemicals. But we will never be as skilled as her :slight_smile:

If you’ve ever worked with beverage and food flavors you’ll see the parallels. Or looked at the “Eastern” school of medicine.

I always wanted to move THC production to tomatoes, but that was a response to the illegal nature of cannabis. It would be much easier to produce cannabinoids in something that already made olivetol (eg HOPs)

With available tools and published data, it would within the capabilities of determined biohackers to produce various cannabinoids in yeast, and any commercial venture to move it into a number of host plants.

Tobacco was certainly an early workhorse for GM plants, but I would imagine there are better options from a production point of view. Rape seed (Canola) would my first thought [cannaccanola]. You could give the kids their CBD in oil with out all the fuss of solvent extraction or formulation. (just squeeze and serve) :slight_smile:

Certainly going back into a 25+% THC cannabis strain and editing the THCA synthase triplication so that it’s now a CBD synthase triplication seems like it would be worth attempting.

But I’m of the opinion that we should save the whales by editing their intestinal micro-flora to enable plastic degradation, so I might be slightly biased towards the whole GMO strategy.

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yea they definitely did some weird genetic research shit with tobacco, i think making an organism glow is like the “Hello World” of genetics research lol
what do you think of a tree whose fruiting bodies r full of cannabinoids, like an apple tree but instead of apples just sacs of keif lol
im mostly joking cause i know it would much harder but still trees seem like the purification biofactory to me. very little maintenance, large year-round output, stabile genetics so stabile profile, easy harvesting. whats not to lik

I think the real interesting application here is for API’s (active pharmaceutical ingredients).

It’s incredibly difficult for researchers to do valid research on cannabis without having access to a large supply of identical plants with a known lineage and repeatable, reliable, uniform chemotypes. This is out of reach for even most pharmaceutical companies - GW Pharmaceuticals being the obvious exception.

However, studying the activity of cannabinoids is not only easy with isolated compounds, but arguably it’s preferable. When someone can kick out and supply isomerically pure bioreactor produced cannabinoids which contain no traces of other compounds, the research game really opens up.

As we’ve discussed above, THCA synthase has already been put into yeast cells and can express milligram quantities suitable for research, now it’s simply a case of scaling this process.

That work is already being done for the process of creating ‘hoppiness’ in beer - specifically yeast bioengineered to produce aromatic monoterpenes. (See here - Industrial brewing yeast engineered for the production of primary flavor determinants in hopped beer | Nature Communications).

It’s really just a waiting game before pharmaceutical processes really take over this industry.

Of course there will always be demand for high quality flower, and high quality dab oil with a full cannabinoid and flavour profile from the bud it was extracted from. And of course hotdog pens aren’t going away any time soon …

But the medicinal market … just watch pharmaceutical companies swallow that one up. I for one can’t wait to have more money poured into cannabinoid/ECS research. Look at what black market breeders did to cannabis in 40-or-so years - took THC percentages rocketing above 20%. Now imagine what pharmaceutically funded and professionally educated biologists could do with CRISPR and a license to play with cannabis. Bring me the 50% THCa flowers.

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So we can like it twice!

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I believe most of those efforts were achieved at great expense and then the only reason at the time as I recall some of those studies were done simply because the federal ban on pot made it impossible to study. So at least some of these efforts to produce THCa by manipulating the genitals of the striped belly dung beetle (biosynthesis) to obtain trace samples to conduct research that could not otherwise be legally conducted.

I have yet to see research that targetted the idea of large scale production. The problem then becomes attempting to engineer what mother nature already engineered AND to do so in an economic environment that no longer makes it necessary to manipulate genes to recover trace amounts. The economic environment at the moment suggests tons of THCa is sitting idle in storage and the street value is far below what legitimate growers can withstand very long.

So the idea then of manipulating genetics to produce a drug that is in huge over abundance would have to present a real advantage otherwise since it could not possibly compete on price. So that leaves marketing… and more to the point marketing against a natural and established product in great abundance which iwll be resisted by those who do just fine growing natural products. What spin could be put on it to gain funding? In this environment I have literally seen people choose one brand of potato over another because one was labelled non-GMO.

This is where the problem will jump up and bite this excellent idea. It takes but one congressman or senator to raise alarm that the natural and proven safe drugs just legalized preclude the need for tinkering with mother nature and before you know it one state passes a law against GMO THCa. Then another. And so forth.

How would you market a drug that has a history of ferocious customer loyalty over the natural, inexpensive, and simplistic to grow medicine and almost certainly would normally be the type to only select non genetically modified products?

In my opinion marketing, traditional MED+REC market saturation, etc, are irrelevant to the most likely applications of this, pharmaceuticals. The barrier to entry for creating a pharmaceutical makes just about all of those variables irrelevant. Unless you want to specifically talk about pharmaceutical distribution marketing.

Also general question, I am a complete n00b when it comes to this topic (adding, replacing genes, etc) but greatly want to learn more. Are there any decent educational resources, even forums I could lurk to learn more about possibly doing this in my garage with some disposable income? I’m learning to parse sequences in R to eventually find genetic markers, but after that I can’t find many practical ways to apply that knowledge. Apologies if that’s a stupid question

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I believe biosynthetic processes will become the norm for producing isolate level cannabinoids to be used in pharmaceutical/nutraceutical preparations. Some B vitamins have been produced this way for quite some time. A number of products will be able to be “customized” by changing ratios of cannabinoids and even terpenes for standardized products.

I don’t ever think connoisseur flower will disappear though for smoking.

You can chew some bark or take an aspirin…

Eventually the majority of THC(A) consumed will not be in flower form, so it wont matter where it was derived. The energy and labor involved in commercial cannabis production is enormous. The expense of agricultural land compounded by the “Agro-gentrification” that occurs in rec States will eventually cause the bubble to burst… If it already hasn’t.

I really dislike the anti GMO arguement, if someone objects to GMOs they probably have very little real information on them. I have made transgenic organisms myself and I have a deep underlying of the subject. My favorite moral conundrum for anyone anti GMO: Should diabetics go back to using horse and bovine insulin taken from slaughterhouses? Or should we just as accept that GMO E.coli which produce human insulin is better and safer? Ie. no risk of mad cow disease.

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Lolz I too could care less where my spuds come from or whether the THC comes from modified organisms or mother nature. The problem is not the technology for such a good idea. The problem occurs because of the association of genetic manipulation with (highly unrealistic) fears that the process could somehow grow out of control of the men who created the “artificial” life processes.

This is the reason I hate so many marketting campaigns is because the effective ones play upon unfounded fears. For instance, back when skunkpharm was just beginning to emerge as the definitive source of current knowledge the majority of users there at the time had fears of solvents like hexane. This was marketted then when any company decided to process without solvents as a safer product because no solvents had been used. Fast forward now to when skunkpharm is still displaying old thumbnails which are broken links of my own youtube vids (purged now by youtube) on their main page and the fear of solvents now is just not a factor anymore really. People got used to the idea.

I think the analogy of chewing bark versus refined aspirin is a great one and the gruesome imagery of insulin production as old vs. new also makes a good point. I would think that a good selling point for the idea would begin with this sort of core notion irregardless of how it is worded. Once folks are used to the idea it should fly if this is indeed a less expensive product. I hope you enjoy good success with this innovative idea and wish you luck. :slightly_smiling_face:

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Research by Some large pharma companys is being done right now to alter the cannabinoids in this plant dono much aboat iT but since iT Is not illagal research is a lot easier

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