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13:45kind of hypothesis, right? It's it's like when you think about it at the molecular level, this is the only way that it could have happened. >> There there can't be a chain of independent processes generating this outcome because it would be the second >> link in the chain >> would not have sufficient information to consistently select for the same side. So, it has to be an endto-end process. >> Yes. that is self-contained from start to finish. >> Yes. And this was in 1973. They had this hypothesis and people have been looking for this enzyme ever since. >> Ah so we have the hypothesis which defines this idea that it has to be a
14:25singular process but we've not seen it experimentally. >> Yeah. We've been trying to look for it. >> These guys found it. >> Okay. >> That is the paper. Okay. This phantom enzyme for over 50 years. It's now been found. The study is out in new phyitologist. um first author Wood very nice paper >> Katherine Wood and the idea this is a 50year-old treasure hunt >> to try and find this thing okay and there are applications that we'll get to later but I think it's just incredible that like there's been the science >> question for 50 years based on a very simple experiment which is that this pathway is not symmetric and the only way it can't be symmetric is as you said
15:07it's got to be an endto-end process >> and one thing that's always so interesting in the modern conversations in the contemporary conversations about science is this idea that we've already solved all of the problems >> andor solving old problems is you know sufficiently trivial. >> Yeah. >> Um and this is a perfect example that's obviously not true. >> It's obviously not true >> but this is a perfect example of that. >> Exactly. And this this paper is also really nice because it uses very modern techniques to answer this problem. We've got alpha fold with AI that we're going to get into later. >> Okay. >> Um new techniques that are only, you know, sort of available now in the
15:47modern day. >> Right. So the target organism that they used in the study is um fluia sufrsa. It's um actually used in Chinese medicine. Yaq I believe is how you pronounce it. Um I got one of my friends who's Chinese to to send me a voice recording. So if that's wrong, that's his fault. um maybe he's setting me up, but it's been used in Chinese medicine and we know consistently that it forms non-ymmetric alkyoid securine. Okay. >> Okay. So, this is now the model organism that we're going to use to try and find what is the enzyme in this plant that is doing this. >> They do um transcriptto analysis. So
16:27they extract the RNA from 15 different tissues in the plant and they do denovo transcryto analysis of the whole thing to figure out what the mRNA is that is being transcribed from the DNA. From that they get a bunch of candidates and they look for what are the enzymes that could be possible that are creating this. They find two enzymes. There's gene 4,984 4984. That's your standard cadaavverine. It produces your cadaavverine which is the intermediate product. >> But then they've got this one gene 1864 >> and that produced your one piperine
17:08which is a precursor of that securine with the alkyoid. It's producing that end product >> in one step. You're not getting any cadaavverine. Okay? You're not getting anything in the middle. And that this is that enzyme that we're going to get into later on. But that's the enzyme that they found. And they found that this enzyme could take you from lysine all the way to the end in one go. >> So the idea is gene4984 was just getting us to in this chart that we're looking at the middle step where the cadaavverine is created, but it did not bring us through the oxidation and then all the way down into >> the sort of final product. >> That's right. But that gene 1864, this
17:52was the smoking gun because it was that endto-end process. >> Exactly. Yeah. And it's the smoking gun, but that's not going to make your paper. >> I see. Okay. >> Because if you just submitted a paper being like, "Hey, we found this enzyme that does the whole thing." >> Well, it could be doing all sorts of other stuff. Reviewer two is going to be like, "Well, you didn't you didn't really show that it's non-ymmetric and and all this other stuff, right?" Yeah. >> So, reviewer 2 is going to get you. You got to go even deeper. You got to really convince your reviewers. >> Mhm. >> That is the thing that is doing that non-ymmetric >> grabbing and how is it doing it >> all this other stuff, right? And so that
18:34they didn't they didn't stop there. Next, what they did was they purified that gene. They incubated it >> and then they wanted to see how how exactly is it doing this. So they got um a lysene and they tagged the nitrogen this time. >> Okay. >> Okay. The nitrogen this time is only going to be on one end. >> Mhm. >> And if it is stepwise, meaning there's an intermediate, then the nitrogen is going to we're going to see we're going to see a nitrogen getting stripped. And so you'll see the final product not have that radioactivity, that radioactive isotope of nitrogen. Or you're going to