Brewing a Revolution with Fungi: The Next Generation of Cannabinoids – Mushroom Revival

Brewing a Revolution with Fungi: The Next Generation of Cannabinoids

Researchers at Hyasynth Bio are brewing yeasts that make cannabinoids such as CBD and THC. Using a method known as Biosynthesis, the Montreal-based team has optimized genetic instructions for brewers yeast to manufacture cannabinoids within their cells. Once the yeasts have propagated enough, they are decanted and the cannabinoids are harvested from the brew. This results in a level of potency and purity not seen in the cannabis industry before. 

Today on our podcast, we have the pleasure of speaking with the metabolic engineer and co-founder of Hyasynth Bio, Alex Campbell. We dive deeper into their cutting edge technology and its implication on the cannabis industry. 

 Topics Covered:

  • Origin story and technology of Hyasynth Bio
  • How yeasts can be used as molecular factories 
  • Metabolic pathways in yeasts and other fungi
  • Perspectives on genetic engineering
  • Farming CBD with microbes, especially yeasts
  • Resource requirements for growing cannabis plants, how that compares to methods in biotechnology
  • Where enzymes for cannabinoid precursors are found
  • CBD, THC and other cannabinoid benefits to human health

Show notes:

 

TRANSCRIPT
Transcribed by https://otter.ai ** Subject to error
Alex D. 0:00
You My friends are listening to the mushroom revival podcast.

Lera 0:04
Today on the show we're discussing yet another innovation in applied mycology. Specifically using yeasts to grow cannabinoids in a bioreactor. This was a juicy conversation, and I'm so excited for you all to hear it. But first, a note from our sponsors.

Alex D. 0:22
Us, you all know the job by now, if you love the show, please support us by leaving a review. And we'll even feature one lucky reviewer on our podcast every single week. You can also go to our website at www dot mushroom revival.com to support your health, your energy, your cognitive function, your ability to deal with occasional stress, you name it, just feeling the best you could possibly feel with functional mushrooms. And we have a special discount code for you pod treat at checkout. For a special surprise discount, we won't tell you what it is. You got to find out yourself. If this is the first time you're listening to the podcast. Welcome to the mushroom universe. And now it's the review of the week.

Lera 1:07
So this one is from Jake num for title very informative review. This is a great podcast to get oriented in the world of fungi. Don't let one source solidify your mindset. There are many sides of mushrooms. And Mr. podcast does a very good job at giving a voice to many of them. Much love. Thanks, Jake. No, we honestly do try to provide a multitude of perspectives.

Alex D. 1:32
There are many sides of the same gem. And now we bring you Alex Kimbell.

Lera 1:54
Alex cambell Thank you for being here. I saw you one of your team members on a fungal biotechnology panel. And I was so cool what you guys were doing. I had not heard of this application before. You are a metabolic engineer and co founder of Hyasynth Bio, where your team is using yeast to generate cannabinoids. So cool. And I have about 100 questions. But to start off, can you tell us who you are? And what is highest? And what are you doing there?

Alex C. 2:27
Yeah, absolutely. And thank you so much for having me. So my name is Alex and I'm the co founder and chief Scientific Officer of Hyasynth bio. And, you know, I have a science background, I was always really interested in science really interested in biology. But it wasn't till until I got involved in something called the International genetically engineered machine competition that I really found what I was passionate about, which was at the time, this relatively new field called synthetic biology, which was the drive to create basically new programmable forms of life. And so iGEM is this really cool competition where you can do it as an undergrad. And basically, you have a team together at your university. And you work together over the course of a summer to build really cool genetically modified organism to do really cool stuff. And people got really creative with this, you know, you had people making bacteria that could produce all these new novel really interesting compounds you how he had people building biosensors, you had people building environmental, remediation organisms, all kinds of really cool stuff. And then, at the end, you go to MIT, you have a big competition and a lot of fun. So that was what really piqued my interest in, you know, this new field synthetic biology. And I knew I really, really wanted to study this. And I got involved with this professor at Concordia in Montreal called Vince Martin, who, you know, runs one of the best synthetic biology labs in Canada. And at the time, one of his projects was working on this strain of yeast that produces opioids. So that's things like morphine coding, oxycodone, lots of really, really valuable therapeutic compounds. And, well, I really, really was excited about the technology. I just thought it was the coolest thing in the world that you know, you could train us to be your own little factory for these really, really valuable medicinal compounds. And, you know, I could just see how much better This was then growing field of poppies, which is how people still get this stuff today. But, you know, I wasn't particularly excited about opioids. And I thought cannabinoids would be a much much better application to this technology which, you know, helps show so many people with their daily life, and even today are still relatively unexplored and untapped and you know, Not at quite the potential that it could be. So from this, the idea for Hyasynth was born that, you know, we should build a yeast strain to apply these benefits to the cannabinoid pathway. So we were formed in 2014 started off with about four really young and eager scientists with this idea. We got hooked up with this venture capital firm called SOS ventures, which is the largest life science investor in the world. And at the time they were running. It's called any bio, and it was the world's first synthetic biology accelerator program. So we got a lot of support from them, some initial capital to start building out, you know, a platform and a proof of concept. And here we are seven years later, you know, we're 20 full time staff, we have our r&d engine fully developed, you know, we have a really expansive IP portfolio. And we're just about to launch our very first product, which is going to be the world's first fully biosynthetic CBD isolate. And if you don't know what isolette is, it's basically the fancy cannabis term for something really, really pure. So essentially, what we have is a CBD, Crystal that's 99% pure that you can drop into your favorite brownie or vapor, whatever you like.

Lera 6:17
Where is there a line there? I mean, if you just tweak a little thing about the genome, Is that considered synthetic in the field?

Alex C. 6:26
Yeah, I think so. Um, I don't know if there's like a hard and fast line between synthetic biology and metabolic engineering would say genetic engineering is a subset of synthetic biology. But, you know, we don't really like to use the word genetic engineering anymore, because it has a, it kind of sounds like a little bit evil and like a little bit. Yeah.

Lera 6:50
Definitely has a bad rap. Yeah, so I had

Alex D. 6:53
another question. But I really want to talk about that, because it does and we non GMO is stamped everywhere. And so people are kind of brainwashed to think any genetically modified organism is bad. I studied micro remediation for a while and you know, that's, that's the use of fungi to clean up toxic waste. In our soils, or or waterways, things like that, and even other sister sciences like phytoremediation using plants to do the same thing. Any industrial application is using genetically modified organisms. And you know, they have an amazing benefit, right? And so sometimes they might be bad, but sometimes incredible. So I'm just wondering, like, how do you navigate that? In terms of wording? Do you have another word that you kind of market it towards? Or is there a lot of education to let people know, like, Hey, this is this is not as bad as you think? Or, you know, how do you how do you navigate that?

Alex C. 7:57
Yeah, so we we typically try and avoid, you know, bringing attention to the fact that we use genetically modified organisms. And that's not due to the fact that, you know, we think this is a bad thing, or that, you know, we think this is a really particularly scary thing. We think it's just not really particularly necessary to what we're doing. Because Well, this is the kind of chassis this and vehicle that we use to make these products. We don't actually have any yeast DNA or biomass end up in our isolette. At the end of the day, we're making really pure chemicals, and there's no trace of these organisms in those chemicals. So technically, we can say that everything we can make is non GMO. So we're trying to avoid that language wherever we can. Right?

Alex D. 8:42
Right. So I'm curious why yeast, I know a lot of people use E. coli. And to produce a lot of novel compounds, their eco is super easy to genetically modified to do lots of things like glow or make some, yeah, make some crazy stuff. And even in psilocybin in the psilocybin industry, I mean, they're using genetically modified eco light to produce large amounts of the pure psilocybin molecule and even cillessen. So is there a benefit towards yeast for cannabinoids or is that, you know, either or E. coli or yeast and they both are great. I'm just curious why you chose the yeast model.

Alex C. 9:26
Yeah, absolutely. So you're absolutely right, that for a lot of systems, like an E. coli or a bacterial system is kind of the way you want to go because bacteria grow way faster than east and they have really fast metabolism. So if you have something pretty simple bacteria are really good at growing fast and making that ton of bed. The issue with the cannabinoid pathway is that a few of the enzymes in it are really, really complicated and poke Harriet's like E. coli have a really Really hard time dealing with it. And especially the last enzyme, so that's usually something like THC synthase, or CBD synthase. That requires extensive protein glycolic, like that. But constellation, which is really only a post translational modification found in eukaryotes. And people have tried to put that in E. coli. And it's just, it seems to be almost impossible. So if you're looking for the simplest organism that can grow quickly, you know, is a model organism that people have been engineering for forever has all these established tools and, you know, people have been producing with these for forever making beer and all these different fermentation products. And that can handle this pathway that is a little bit more complex biologically, yeast is the way to go for sure.

Lera 10:54
Is this is what you're doing considered molecular farming? In a way,

Alex C. 11:00
molecular farming? I'm not sure I've heard that word. Is that similar to cellular agriculture?

Lera 11:08
Yeah, it's like it's something I was interested in, because I saw paper months ago that was like molecular farming with Agaricus bisporus, which is the button mushroom and it was farming with a Ph. And basically it's you're farming drugs or some kind of molecule using a host I imagine that's either genetically engineering it to produce that or feeding of certain foods so that it's a waste product is the thing that you're after. But, you know, that's probably just niche terminology there.

Alex C. 11:39
Yeah, I've not heard that term, but I actually like it a lot. Because that basically is what you're doing right? Like, right, it's like these little tiny microscopic yeastar you know, your cattle or your pigs and, you know, you're you're milking the CBD or the THC or whatever you want out of them. So I've not heard that metaphor, but I do like it.

Alex D. 12:00
Have you heard of Hamilton's pharmacology? pharmacopoeia? pharmacopoeia? Sorry?

Alex C. 12:07
I don't think I have actually, what is that?

Alex D. 12:09
Oh, you should look it up. It's a great show. Hamilton. Morris is the host. And he has an episode. Have you heard of Bufo frogs? Or toads,

Alex C. 12:21
Bufo toads? I don't think

Alex D. 12:24
they have. they secrete a psychoactive compound from their backs. And so people have been using it for a while, but it's gotten really popular. And so to get this psychedelic drug, you have to kind of string up these toads and stress them out. So they secrete this toxin and you scrape it off their back. And, you know, that is the preparation for this psychoactive drug. And, you know, in the show, he covers the whole episode, and he and he's like, he basically makes the case, you know, we should use the pure chemical of this and not harm these toes anymore. And I'm just curious, I want to, you know, make the analogy, have you made the analogy of like, you know, let's stop growing fields and fields of poppy, if we can just make it easier in a lab? Would you say it's more sustainable to cultivate yeast in a bioreactor and make 5,000x more CBD per square foot? Or is it a fraction of the time? Is it you know, more ecologically sustainable? Like, what's the case of growing it in bioreactor versus growing cannabis? Or hemp in the wild?

Alex C. 13:40
Yeah, absolutely. So we tend to face a really common problem when we're trying to access a lot of these really valuable therapeutics, where we have a natural source that is not particularly efficient. Like, you know, in the case of that Toad, you know, it's, you know, you want your pure molecule, but you don't want to harvest it by a toad, which is just really inefficient. And, you know, I can think of a parallel with something like insulin where, you know, up to almost the 1980s people are harvesting their insulin from pig pancreas, which is a terrible way to get insulin and just really, really crazy, efficient and like, you know, that was the 1980s. Like, that wasn't that long ago? No. And the solution to that was this company called Genentech, which is today one of the world's most successful biotechnology companies. And essentially what they did was basically using, you know, very early metabolic engineering and synthetic biology. They train this bacteria to basically eat sugar and poop out insulin for them, which is just so much more efficient than killing a bunch of pigs if you want this stuff, and so we're doing The exact same things but for cannabinoids, so instead of having to grow these huge, huge fields of hemp and cannabis that just scratch on to the subset, we've got a really simple process. It's a lot like brewing a beer where you just have water, sugar and yeast. And you know, when about seven days, you have this huge batch of Eastern, you have a big use pellet that's just filled with CBD that then you can purify out. And, you know, sell is a really pure ingredient. And you know, it's really, really cheap, it's cost effective. It's really, really environmentally friendly to, a lot of people don't realize this, but growing cannabis is actually quite environmentally intensive. And doing biosynthesis actually results in about a 90% reduction in land, water and energy uses versus traditional cannabis agriculture. So it's a green product, and it's just really clean to you know, it's just so simple. There's no heavy metals, no pesticides, no agricultural contaminants, you don't have to worry, you know, the only thing you have to worry about is getting a little extra sugar in your product.

Lera 16:13
This, it's amazing, and it feels like the metabolic future. And because you are a metabolic engineer, which I think is super, super badass, do you think that this method of farming a molecule can, in theory be applied to any, like, medium weight molecule out there?

Alex C. 16:33
Yeah, pretty, pretty much anyone, wherever there exists a metabolic pathway, there exists the opportunity to teach something like yeast, or like eco light to make this. So things like psilocybin, like you mentioned, you know, LSD, opioids, any kind of really complex pharmaceutical product, this has the potential to be introduced to a microbial host and just made so much cheaper. And there's a lot of really, really complicated natural products, things like taxall, you know, things that exist in these trees that are like, you know, 50 steps if you want to do it by a chemical synthesis, and biology can really help out there. Because we can use these enzymes that nature has already built as a manufacturing template to make these molecules and they make them exactly to spec You know, they're exactly, exactly the right stereochemistry they're exactly the way they need to be, you know, they have all the functional groups in the right place. You know, we can really use what nature has given us to produce produce a lot of these really valuable therapeutics that are hard to access in other ways.

Alex D. 17:44
Right, I'm going to give you another show that I love so much. It's a documentary series called pain plus poison. And one of the episodes they did they had a spotlight on penicillin. And penicillin is production. And they went through this challenge of Okay, how do we produce? How do we grow this fungus it on a mass scale to produce these compounds and they were growing them in like these little glass jars and then turning them on inside and kind of harvesting the mycelium and the exit days? And then they actually figured out okay, we could make bio reactors and the first one is in Brooklyn, and it's kind of a historical site although I think they shut down the factory now but it was the first site of bio reactors bio reactors producing penicillin. And I'm just curious that was a beginning introduction to the question of Have you noticed since the beginning of of launching this company, have you noticed bio reactor technology you know, exploding it seems it sounds like you can, you know, grow microbial organisms to produce whatever compound ever. So it seems like the the use case is exponentially, you know, through through the roof important. And the second part is like, where do you go to learn about this stuff? Are there expos I mean, do you go is there an expo all about bioreactors? Is there a magazine you could subscribe to? Is there Facebook groups, like, you know, where do you go to get the latest bioreactor technology or to learn that the latest, you know, things about bio reactors and bio engineering microbial organisms?

Alex C. 19:44
Yeah, absolutely. So we're actually pretty lucky in that, you know, yeast is like, Penicillium mold is insanely tough to culture in a bioreactor. It just doesn't really go into liquid culture now, so we need to use these really weird Culture methods on it. And we're very blessed to be working with these because, you know, yeast is the model organism, people have been brewing with yeast fermenting with yeast, for 1000s and 1000s of years, and people really know, we really figured out exactly how the fermentation technology needs to be. And, you know, I don't think it's changed too much in at least the time I've been active. But, you know, we really have at least culturing yeast, you know, down to an art. So like, we don't need to rely on too much in the form of innovation there. But yeah, you're right, bio reactors are these really, you know, complex vessels. And sometimes, it can be difficult to know, where to go to figure out, you know, if it's your first bioreactor, what model Do you want to get, like, how many ports do you need? You know, how do the control and the tubing. And you know, for that, we've had really good scientific advisors that we've relied on a lot. And you know, also, the vendors that sell this stuff are very receptive, as well. So places like Apple con, or Sartorius, if you call them, they know that, you know, their product is really tactical, and they're really responsive and helping you figure out what you need and getting you exactly the right system.

Lera 21:22
So on this topic, I'm kind of curious what you can tell us about, like, what's actually going on in your tanks? Like, do you brew the use for a while and then remove all the liquid and spin it down and separate? The resulting liquid? I don't know if you can tell us any of this. But I'm, I'm curious to kind of put a visual in my head.

Alex C. 21:42
Yeah, absolutely. So it's, it's really, really simple, actually. So the CBD we make is actually inside of the cell. So all we need to do is go are you stuck to a really, really high cell densities, our CBD is going to be right inside the east. So then what we do is basically decamping East so we'll take off all the liquids. And then we extract that into an organic solvent, which basically blows up the yeast and transfers all the CBD into this organic solvent, which then you can then dry down and purify by a number of different methods. So it's actually a really, really simple, easy process.

Lera 22:22
So is the yeast cytoplasm just full of cannabinoids?

Alex C. 22:27
Pretty much yeah, it's

Lera 22:29
biomass. Like I'm so curious. I don't know. Yeah, it's

Alex C. 22:32
um, you know, it looks like normal yeast biomass. But, you know, I, the cytoplasm, and I assume the membrane as well, because cannabinoids are really hydrophobic is, you know, just packed with these compounds that, you know, you just need to add an organic solvent and you got them right there.

Lera 22:50
So cool.

Alex D. 22:51
So from 2014, until today, which is September 13 2021, at a time recording it sure it's been a roller coaster as any startup, especially biotech. This is, you know, a new new thing. It sounds very complicated. Although I did just catch you say it's an easy process. But I'm curious, like, what have you had a darkest night moment where you're just pulling your hair out? And, you know, wanting to quit? Or maybe many of those nights or days? What do you think? Is that been the most challenging part of growing Hyasynth?

Alex C. 23:33
Yeah, there's been a lot of challenges. So I think one of the major ones has been that Hyasynth was basically a company that me and a few other really young scientists started right out of grad school. And I think people have this idea of startups in their head where it's kind of based around computers in Silicon Valley where you can have one guy and he's got like a $2,000 laptop, and, you know, with a $30,000 budget, he can go build the next Facebook and, you know, be a bazillionaire. But biology is a lot more difficult and a lot more capital intensive. We need a lot more than just a laptop or a laptop to do our work, right. So you know, we need very expensive mass spectrometers to look at this stuff. We need lots of bio reactors to demonstrate, we can have the process that has this rate, you know, if you want to have something that has a reasonable degree of throughput and know you need automated robotic systems to help you build that scale, it's a lot of really, really, you know, more money intensive operations. And of course, you need talented scientists, which have, you know, PhDs to help you build this stuff. So coming out of grad school, you know, being really young. I think it's been difficult to kind of raise the funds we need really show that, you know, we can make this at scale and we can actually produce this stuff. And, you know, we started off, I think our first round was something like, you know, $30,000. And we've had to, you know, show success and show that we can live up to our promises and make everything we can. And it's been a long road, but it's been exciting. And today, our most recent round was about $10 million with Canadian company called Organa gram, which is one of the largest producers of cannabis in the country, which is really exciting. And, yeah, we have a really exciting platform and orangey platform. And yeah, we're doing really good today.

Lera 25:44
And I love your website, by the way, I was just showing some people work like, Oh, this, I love the animation and how clear you deliver the message to the viewer. So I think you guys are doing great. And like I found you on a fungal biotech panel. So it sounds like you're getting the attention and the PR that you deserve, which is super great. On the flip side to Alex's question, do you have a highlight or a past high that you want to share? Like what what has been some of your greatest successes so far in the past seven years,

Alex D. 26:19
that you had to pop champagne for throw a party?

Alex C. 26:23
Yeah, there's, um, there's one moment that stands out, in particular. So I would say the thing that I'm most proud of, and the thing that excites me most is a lot of Hyasynth intellectual property is built around this really, really cool enzyme, which doesn't come from cannabis, it actually comes from basically a slime mold. And it's really interesting because it can do you know, the cannabis pathway to perform it is like a number of enzymatic steps. And this enzyme basically does like 10 of them all at once and spits out a product that is like super, super close to what would be a terminal cannabinoid. So you know, we were really excited about this enzyme, we said, you know, the native enzyme, it doesn't quite make what's in the cannabis pathway, but we think we can tweak it, we think we can engineer it, we think we can make it work. And, you know, we knew that getting this to work would have so many applications and be just such a massive step forward in getting the overall platform to work. And so, you know, we did a bunch of engineering on this enzyme to get it to work and nice, right? And when we finally got it working, it worked better than we can even ever better than we could ever imagine. It was producing that basically, you know, 100% of its theoretical capacity. We were getting great yields of our cannabinoid precursor and yeah, I remember the day we got those mass spec results. I was just over the moon. I had a big smile on my face. Oh,

Alex D. 28:01
hell yeah.

Lera 28:03
So how did you know about this enzyme? Like who thought about it? Like it's a slime mold enzyme. I'm just so curious who spotted it? And then how did you get it?

Alex C. 28:16
Yeah, so that was me. I spotted that enzyme. And, yeah, so the story of that is basically one of the major challenges in working in cannabinoid biosynthesis that we've been aware where from the beginning, is that there's very few enzymes that actually do these reactions, like a lot of other naturally occurring metabolic pathways have homologues and, you know, dozens or hundreds of different organisms. But the cannabinoid pathway isn't really like that, where basically you have you know, cannabis and hemp, you know, it's really closely related kind of brother species, being really the only two organisms that can produce this stuff. And a lot of the enzymes that are responsible for cannabinoid biosynthesis, of which there are not many have a bunch of intellectual property filings around them from companies that are not really in the biosynthesis space. So this was an issue we were really aware of by the beginning and really wanted to work around. So from the beginning we were really on the lookout for novel enzymes that could potentially a not only work better in yeast, because you know, the cannabis enzymes are plant enzymes and you know, they're not particularly happy in these because that's not where they evolved to be and not where they want to be. So both enzymes that function better and kind of gave us that, you know, freedom to operate and ability to kind of actually work in the space without stepping on all these patents and You know, basically we discovered this kind of from a more obscure academic source, this enzyme was making something called nppd, which is this signaling molecule that the slime mold called mycelium uses to you know, sense lots of stuff in its environment and control its lifecycle and different things of what it's doing. And we noticed that this molecule was really really similar to something called off torque acid, which is the main precursor for most cannabinoids. And so, seeing this, you know, we had this idea that, you know, if we could only engineer this enzyme and remove this one part of it that was adding this little piece onto all of folic acid that we didn't like, you know, we're gonna have this just amazing, amazing enzyme that could do all this really cool stuff for us. And so you know, we hypothesize we could tweak it and use to make it produce this this compound that we wanted and we were ultimately successful in that and then that was a very, very happy day.

Lera 31:05
Such a cool story. Thanks for that. Shout out to the slime mold kingdom to

Alex C. 31:11
Yes, time all day, it might be my new favorite organism. Very, very pleased.

Alex D. 31:15
They're fun. Definitely. Yeah. So I think a lot of people have heard about CBD, it seems like it's been the hot buzzword for quite a few years now. And especially with you know, globally things getting a little more stressed out. I think more people are reaching for CBD and quite a lot of other things. But do you want to give just kind of the quick one on one on why CBD and why, you know, maybe this is different from some CBD you might find at a gas station or you know, because there's there's very, there's varying levels of potency in the CBD market, a lot of snake oil, a lot of bogus stuff. So just kind of lay down the benefits and you know how you guys are different?

Alex C. 32:12
Yeah, absolutely. So I think what CBD a really good place to start is with the the story of a little girl called Charlotte Fiji who was really responsible for kind of bringing the benefits of CBD to kind of into the focus of the public knowledge. And she was this little girl about 10 years ago who suffered from something called gravity syndrome, which is this really, really bad neurological disorder that causes really severe epilepsy. So she was having about 300 seizures a week, which, as you can imagine, must be just really, really unbearable. You know, she couldn't eat, she couldn't talk, you know, she's almost catatonic at this point. And so her parents tried pretty much everything because, you know, you can only imagine seeing your your kid in such a state. And they tried, you know, every day in the block. They tried all these pharmaceuticals with really intense side effects. And nothing helped nothing could reduce the seizures. And then as a last resort, they said, Why don't we try CBD. And, you know, it was basically like flipping this switch where before she was having 300 seizures a week. And then after she started taking it that was down to like, two or three a month. And you can only imagine the quality of life improvement that that provided. And so this was about 10 or 15 years ago. And it was a really huge story at the time, it made the national news. And it really helped popularize CBD and a lot of the medical benefits it brought, because a lot Not a lot of people really knew or understand stood much about what CBD did. And you know, at the time, there was only one high producing CBD strain and it was called hippies disappointment because people were just upset that it didn't have THC and it didn't get too high. They didn't really understand the value of CBD. And so that story is kind of responsible for raising people's attention on CBD and what it does and getting people to study a lot more of the benefits of what it does. And you know, it offers a lot more than just kind of this pharmaceutical grade epilepsy treatment. It has a lot of applications for you know, normal people like you and me where you know, it has this really interesting interaction with the endocannabinoid system. And I guess to give you a very long winded answer, you know, I need to explain the endocannabinoid system a bit, which is this really, really cool regulatory A system that we have in our bodies that not a lot of people really know that much about or talk about that much. But you know, it's not just found in humans, it's found in pretty much all animals. It's found in cats, it's got a dog, it's found in even invertebrates like slugs had that it's really, really essential to most macroscopic life, it seems. And essentially what your endocannabinoid system is doing is helping to regulate your nerves, your neuron, and your nervous system. So if you take an example of something like pain, you know, you do something dumb, you stub your toe, and you know, instantly your nerves send a signal to your brain that says, hey, you know, I'm in pain, I don't like this, you're dumb, we should stop doing this. And you know, those pain signals are are really, really important because they give us really valuable sensory information about the world. And it's important that they turn on, but it's also really important that they turn off to, which not a lot of people think about, and you know, if I stub my toe, I don't want to be in pain for weeks. Like that's just not productive. So we need a new way to regulate the really complex activity that's going on in our nervous system. And cannabinoids are a really integral part of that regulation. And, you know, basically, you know, when your body activates its endocannabinoid system, it will trigger this response where basically

you know, there's inhibits the neurons that kind of firing a lot of these sensory pathways and it's basically a way of turning down the volume on a lot of the really intense sensations we feel like pain. And you know, it's not just limited to pain. The endocannabinoid system is just massive throughout your body. The Endocannabinoid receptors which kind of govern this are the most common receptor in the human body, which kind of goes to show just how important this system is. And it regulates pretty much everything from sleep, anxiety, appetite, mood, even immune response. And you know, your body has its own way of activating this through things called endocannabinoids. But as you guys might have guessed, there's a much better, more efficient way to activate this. And that's found in you know, these molecules inside cannabis, THC and CBD. And so both of these can activate your endocannabinoid system. Each of them binds to a different receptor in the endocannabinoid system, which, you know, explains why they have different effects and why one makes it feel kind of funny and one doesn't. But CBD in particular, is really, really helpful at doing things like improving sleep, reducing anxiety, improving mood, it also plays a role in regulating appetite. And I think pretty much everyone in the planet has had some interest in improving their their response to one of those factors. So CBD is something that is really really useful for a lot of people I think.

Alex D. 38:25
Great and I'm just curious what your I don't know if you can share this but maybe 510 year plan Do you plan to go beyond CBD to other cannabinoids? Like potentially THC or no, you know, CBG, CBC, CBD V, or any, like terpenoids you know, I know there's a lot of talk about the entourage effect. And you know, all these compounds are working in conjunction together having an increased benefit. So is that in the plans for your company? hyson

Alex C. 39:06
Yeah, absolutely. So one of the really nice benefits of doing things that way that we're doing them is because we have really precise control over the genetics of our new strains. We can make pretty much any cannabinoids so you can know we can make THC just as easily as we can make CBD. And we can also make the rare cannabinoids just as easily as we can make that so but most people think of cannabis they think of THC and CBD but there's actually over 105 different active compounds inside the cannabis plant, most of which are really under studied just because there's not really a way to make them effectively right now. And that's something that we would like to address. So long term I would like to make all the cannabinoids but you know, we're starting kind of with CBD and then we Have a few minor cannabinoids that I'm really, really excited about that, you know I think will be targets for us over the next couple of years. So one is this molecule called THC V, which is really, really similar to THC. It's just made with a slightly different chemical precursor. So the alcohol trail on it is a little bit shorter. And as a result of that chemical difference, it has kind of a unique profile of effects. It is psychoactive like THC. And it's a really unique psychoactive compound that, you know, it said it's a lot more euphoric, and like more high energy than a typical THC. And then the other really interesting thing about THC V is that it's also an appetite suppressant. Whereas most cannabinoids act as appetite stimulants, and you know, this is really cool if you know if you've ever had the experience where you've maybe consumed too much cannabis and then gotten really hungry and eaten a whole cheesecake and then thought, Oh, that was not such a good idea. It is

Alex D. 41:06
probably the worst of your problems. Yeah, you're not you're not gonna beat your family when you come home, you're getting some cheese cake.

Alex C. 41:16
Yeah, it's not the worst side effect. But you know, if you if you like your cannabis and you know you don't like having those experiences. THC v could be for you, you know, it could be this really cool diet, we diet cannabis. I think it's really exciting. Two other compounds that I'm really excited about that, I'll just go into really quick. One of them is CBC, which is a kind of double cannabinoid cyclization. So THC and CBD differ by their cyclisation. And CBC is just another version of that cyclisation. So it's similar to THC and CBD. But, you know, a few of the molecules are just a little bit rearranged. And CBC is really cool because it's a really, really strong anti inflammatory compound, probably even more so than something like CBD. And as a result, I think it's going to be really, really valuable for a lot of people, both as a cosmetics and topical ingredient. So we look at something like a cosmetics cabinet, our cabinets are actually great, because they have these anti inflammatory properties, they reduce redness in your skin, they reduce itchiness swelling, they just have your skin looking really nice, they fight acne. And that's why you see them in so many, you know, face masks and serums and all this kind of stuff. And then the other use would be in something like a topical, you know, something like an icy hot, you know, your muscles ache in something like CVC I think would be you know, perfect for that kind of product. And then, you know, just the last molecule that's that's on my mind that I'm really interested about is CBD V, which is also similar to CBD. But you know, it has that slightly shorter alcohol chain similar to THC v. And it maintains a lot of the same properties as something like CBD, but it has a few cool applications, particularly on the pharmaceutical side, people are finding it's really, really useful in treating things like some of the social inhibitions and repetitive behavior that can come in things like autism spectrum disorders. So it has a lot of really, really cool format application, it seems. But you know, that's just the beginning the rest just three, I really like it three I'm really excited about but you know, there's hundreds of these and people are just really beginning to understand, you know, what these things do and what they're used for. So

Lera 43:55
I just have a another kind of tech question for you. If you are going to create these other cannabinoids, in terms of the technology, do you change the enzyme or the precursor? Or both?

Alex C. 44:11
Yeah, that's a great question. It's depends on what you're making. Exactly. You know, some of the enzymes are promiscuous. So if you feed them a different precursor, they still work the same, but they make you a different molecule. Some of the enzymes are less promiscuous. So you know, you need to have a whole new enzyme for that particular molecule. Or you need to use something called enzyme engineering to change your initial enzyme into something new, something that is new and something that has that activity. And that is a really, really cool and versatile technology that Hyasynth uses that lot to, you know, either improve the performance of an enzyme, or given enzyme a totally new activity. So it depends a little bit on what you're making. There's different strategies and sometimes you need to mix and match.

Alex D. 45:04
Very cool. So I I'm a consumer and also a business owner so I for listeners who might be one or the other both Where can they see Hyasynth in the future would you have a direct to consumer product where you know you have a branded Hiaasen, you know, CBD products or cannabis products or if say I own a, you know, cannabis line or a CBD line? Can I purchase isolates from you in the future? Or, you know, is this gonna be I know a couple brands were cool, you could do like a quiz. And they make a vitamin pack for you so similar, like make your own strain of Oh, I because of this quiz, I need 75% of this compound and 5% this compound and this where do you feel like you guys are going to go because there's I feel like this applications huge. Yeah,

Alex C. 46:09
yeah, so I think we, you know, we don't really see ourselves in the consumer space right now, we would like to start off as being able to provide these really, really pure really, really high quality biosynthetic isolettes to businesses, because I think that's actually a pretty big need in the market right now. Like, if you look in the US, there's certainly a lot of CBD on the market. But you know, there's lots of problems that they're facing with the supply chain right now. And part of that is based on you know, that hemp and cannabis and the way that people traditionally make this stuff is really variable and kind of non ideal to creating these really precise dose consumer products. And you know, if you look at something like hemp, you know, it's a really complex plant that can, you know, has really different concentrations of CBD and THC and no minor cannabinoids, and all these terpenes that are all very strange a strain, and can also vary due to environmental factors that are really difficult to control, like, you know, soil, you know, humidity, temperature, sunlight, all of these things. And as a result, it's really difficult to develop, you know, a reliable supply chain based off of this. And so, you know, in 2020, when the FDA was analyzing CBD products for quality in the US, you know, they looked at 200, and they found that of the 200, they looked at only 10% were accurately labeled for CBD, which is a really huge problem. Yeah, and probably even more concerning than that is 50% of things that were supposed to be just CBD products actually contained THC. Which Yeah, nobody wants that. Nobody wants to see

Alex D. 48:15
when it's the same in the functional mushroom space. I mean, so many things are labeled mushroom, there's not a single mushroom inside or it's the wrong mushroom. It's it's all over the place all the time. Yeah, it's all over the place, or just the wrong Latin name. I mean, it's Yeah, it's so it's it's refreshing to to have some sort of regulations, some, you know, stewards in the space that actually take it seriously and do it by the book and do it really well. Because we need it

Lera 48:47
and I imagine you guys are going to make this so much more accessible. Like perhaps the the reason people are mislabeling things is because they can't get affordable CBD. But I would imagine with your technology, you can buy exponentially more CBD than what you could sourcing from a farm.

Alex C. 49:06
Yeah, that's exactly it, you know, like, with the way we make it. It's both a lot cheaper than an isolate, you get from, you know, a typical hamper or cannabis plant. And it's also really, really consistent and really high quality and you don't need to worry about things like does my isolate have THC in here? Because our yeast doesn't have a THC simply, isn't it? So that's not really an issue for us. And for people who are that's a really big concern. I think that's really important. And, you know, there's also lots of jurisdictions worldwide, especially in Asia where you know, you have CBD being legal about THC being really, really illegal and, you know, really strict penalties if you're caught importing any quantities of it. And I think especially for places like that, our technology is just really, really valuable.

Lera 50:01
Yeah it's really awesome what you guys are doing and shout out to yeast you know we rely on that organism for so many of our goods and our lives would not be the same without it.

Alex C. 50:12
Yeah, it's the best you know it does beer it does bread it does. You know cannabinoids. Now it does pretty much everything.

Lera 50:21
Any snow used? It's delicious. Yeah, so versatile and cooperative, which, you know, that's great.

Alex C. 50:28
Yeah, and the thing. This is such a minor thing, but the thing I really like about yeast is it's probably the only micro organism that smells good.

Lera 50:40
Oh, you're so right about that, though. I yeah, I work with some bacteria. My other job and the only thing I actually look forward to smelling is the yeast.

Alex C. 50:50
Yeah, I smoked a lot of bacteria in my day, and it all stacks but you know, he's just perfect.

Lera 50:59
Totally, I love it. There you go.

Alex D. 51:02
Well, we'll end on that.

Alex C. 51:06
Yeah, it was a pleasure talking to you guys. You got a really cool podcast.

Alex D. 51:09
Thanks. Thanks. Big thanks once again to our Kimbell and all the folks out there pushing the boundaries of how we can partner with fungi. As always much love made the spores will be with you.