1,196 words · auto-generated from the episode video
1:54stories. >> Yes. So, let's break down what exactly is going on here in this new study from the University of York, which was published on January 13th. That's right. And you know, plants are not as sexy, let's say, as you know, animal cells or like bacteria, fungi, but they're incredibly versatile. They've been around for 450 million years. And they've had to deal with a lot over those 450 million years, right? Because they don't really move around. And because they don't move around, they can't do tra traditional defenses of just like running away from something that's trying to eat you, right? They're fixed in place and so they still need to
2:35evolve defenses against herbivores, pathogens, insects that are trying to eat them. And their solution is effectively chemical warfare. Okay? And they're really, really good at chemical warfare. And the core chemicals that we're talking about in this study are something called alkyoids. So they're nitrogen containing secondary metabolites. By secondary metabolites we mean like you know it's not actively involved in photosynthesis and stuff like that. It's a derivative of those compounds and we're aware of these morphine nicotine caffeine quinine. These are all alkyoids that are made by plants as defense mechanisms that they
3:17figured out through their evolution. Right? And this particular study that's out of the York University, it solved a 50-year-old mystery about how exactly certain plants make these compounds. Okay, this idea of alkyoid synthesis. They found the gene that does it for a particular pathway and that could lead to cheaper pharmaceuticals, a lot of really cool things. And I think the chemistry in this particular study is what I found really cool because they've they've figured out the nitty-gritty mechanism by which this particular enzyme does what it's supposed to do. >> So we're going to understand and learn how plants
3:58generate and syn synthesize these alkyoids which they use as a defense mechanism but as humans have some potential commercial applications. >> Exactly. Yeah. Pharmaceutical applications all of that. So first let's just try and appreciate the target molecules right these alkyoids they are heterosyclic rings with a nitrogen by heterocyclic that means there's a cycle of carbon atoms but one of the carbon atoms has been replaced by nitrogen they all come mostly from amino acid there's a few that come from the nucleic acids but most of them are derived from amino acids there's two different types that we can think about there's the lysine derived which are from the amino acid lysine and then there's ornithine
4:40derived compounds. Nicotine probably one that's very ubiquitous. That one comes from ornithine. The idea is you take ornithine which is this amino acid. It's a linear in chain and then you remove some stuff, you add some stuff and you put it into a ring and that ring form becomes then nicotine. Okay. So why are plants even doing this in the first place? Right? Nicotine, for example, very specifically, is something that mimics neurotransmitters in animals, specifically in insects. It paralyzes them. So, if there's an insect that's trying to eat this plant, it can't do it anymore, >> right? >> But because of, you know, animal
5:21evolution, that particular neurotransmitter in insects is also related to stuff that we use in our brain, specifically acetylcholine. Here you can see the nicotine molecule and the the acetylcholine molecule, right? The shapes of the two are kind of similar, >> which means that when nicotine goes inside our brain, the acetylcholine receptors, which are things are receptors on our neurons that recognize acetylcholine and then open up ion channels to then turn on or turn off a neuron. They could sometimes be triggered by nicotine. This is what leads to the cognitive effects of nicotine. You know, the the high that you get or the addiction. All of that is
6:02just because the Lego block of nicotine is closely mimicking the Lego block that is acetylcholine. >> Got it. Right. >> Got it. Yep. Amazing. >> And so that's why plants sort of have an advantage when they evolve these types of molecules, right? >> And a lot of these types of molecules can be used in pharmaceutical research. >> Okay. >> Okay. Now the question is how exactly do plants make this happen? Because remember what I said there's an amino acid which is a linear chain. You usually have like an aman group a caroxile group a carbon in the middle and then some stuff attached to that
6:43carbon. It's a linear thing. You got to now turn this into a ring. Okay. There's several ways to do this at a molecular level, but it's been kind of annoying to figure out how exactly that happens. >> We understand conceptually how to do so. >> Not naturally in the inside a plant or how plants naturally do. So, we can get it conceptually, but we've not yet >> been able to identify how plants do it >> in a non-manufactured way. >> Yes. Yeah. Yeah. Exactly. And so one of the tools that you can use is something that goes back for at least 50 years. It's something called radioisotope
7:23tracing. What you do is you replace the carbon atoms that you grow this plant with with carbon 13 instead of carbon 14 or sorry carbon 12. Carbon 12 is six protons, six neutrons in the nucleus. Carbon 13 is the same number of protons six but you have an extra neutron. >> Okay. >> Okay. And when you you know let's say we supply the the plant pathway with a bunch of glucose that is only carbon 13 right now we can trace how is that plant going to break up this glucose and incorporate it into different types of molecules for example pyuvate or the citric acid cycle. How much of it is going to go into fatty acids right and
8:05we can figure out by weighing the fatty acids and the citric acid and things like that. We can be like, well, the citric acid is only half as heavy as it would be if >> all of the carbon 13 went in there, right? Because it's got three extra neutrons instead of six extra neutrons, things like that. So, that's the logic behind this idea of radioisotope tracing. It's been used to figure out that DNA is the genetic code of life. If we go back to our Watson and Crick episode of last year, >> right? And so the question now is we'd like to apply this technique to how do plants make these alkyoids. Okay. Now let's let's start with the substrate
8:46lysine which is the amino acid. Okay. And this lysine is going to go on to make like anabosine or securine some some alkyoid that we're interested in. Okay. >> The problem is the following. When lysine gets goes through and becomes this alkyoid, there's an intermediate compound called cadaavverine. >> Okay, here's the idea. Lysine is not symmetric because you've got an amino group on one end. That's the H2N, the