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Trp operon

The Trp operon plays a crucial role in tryptophan production, an essential amino acid. In E. Coli, the operon consists of genes and regulatory DNA sequences, including the promoter and operator. Tryptophan acts as a co-repressor, binding to the Trp repressor and inhibiting transcription when abundant. Additionally, feedback inhibition occurs, where tryptophan directly inhibits enzyme activity. This regulation ensures efficient resource use and tryptophan biosynthesis. Created by Sal Khan.

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Video transcript

- [Voiceover] Two of the most studied operons are the Trp operon and the Lac operon and what I wanna do in this video is focus on the Trp operon, which is essential for the production of tryptophan, tryptophan, which you might recognize as an amino acid often associated with Thanksgiving and turkey dinner, but tryptophan, as all or most amino acids are essential for creating the polypeptides, the proteins that you use in your body and so the Trp operon, and here we're going to be talking about not your body, or we're going to be talking about something that's in your body. We're gonna talk about E. Coli. It is an operon that is on the E. Coli that is part of the E. Coli genome, and just in this diagram, the way it's drawn, it would be sitting, it would be sitting right over here. And just as a reminder, an operon is a combination of a set of genes, as well as the regulatory DNA sequences for that set of genes, in particular you have the promoter, you have the operator right over here. The promoter's where the RNA polymerase binds and would start the transcription process. The operator's where the repressor binds, and this is going to be essential for understanding how the Trp operon works. And so what are these genes actually code for? Well these genes code enzymes that are used in the construction of tryptophan, and I'm always amazed that enzymes can be used to construct what are essentially molecules that are much smaller than the enzymes themselves. In fact the enzymes involved are made up of amino acids, but then they're used to make particular amino acids, and so Trp E, D, C, B, A, they're all, once they are transcribed into mRNA and then translated into ribosomes, these enzymes are used to create tryptophan, for tryptophan biosynthesis. So let's think about how this works. So, if we are in a low tryptophan environment, our E. Coli, it needs tryptophan, it needs that amino acid as a building block for its proteins. So in that world, it makes sense that in a low tryptophan environment, the RNA polymerase can just latch on to the promoter and begin the transcription process, transcribe these five genes into mRNA which then can be translated into those enzymes and they you will have more tryptophan biosynthesis. That makes sense that you wanna create tryptophan if you're in an environment that does not have a lot of tryptophan. But what if we did have a lot of tryptophan? Well if you have a lot of something around, you shouldn't waste energy creating more of it. You have to appreciate that all organisms that are around today are the byproducts of billions of years of evolution and they've learned to be very careful, or the ones that are selected for tend to be the ones that don't waste resources, and so when you have tryptophan around, you probably don't want this transcription to occur. So it makes sense that maybe tryptophan can act as a co-repressor for a repressor molecule, for a repressor enzyme, that would attach to the operator and block the RNA polymerase from transcribing, and that's exactly what happens. So if you're in a high tryptophan environment, and tryptophan obviously does not look like these little yellow quadrilaterals over there, but that's just for our visualization purposes, and neither does RNA polymerase look like that, or neither does the Trp repressor look like that, in fact I encourage you to web search these and see how they actually look, they're fascinating. But when you have a lot of tryptophan, the tryptophan can act as a co-repressor, it can bind to the Trp repressor essentially activate it so that it'll change its confirmation so that it can then attach to the operator in the operon, and once it's attached to the operator, well then the RNA polymerase can no longer move forward with transcription. So as you can see this is a very valuable feedback loop, or not even necessarily feedback, if you're in an environment with a lot of tryptophan, don't create tryptophan, or if you just have a lot of tryptophan laying around, don't create more tryptophan. If you don't have tryptophan around, well then the repressor won't be co-repressed, I guess you can say, and then the tryptophan will actually be created. Now, tryptophan's an interesting thing because the control of transcription isn't the only place where you have some type of a feedback loop or kind of a conditional situation. You can actually have direct feedback inhibition between the proteins, and so this part isn't related to the transcription, but if this is a precursor of tryptophan, it's all very abstract in this diagram, and let's say Enzyme 1 turns into Precursor 2, Enzyme 2 turns into Precursor 3, and Enzyme 3 turns in into tryptophan, well you actually have direct feedback inhibition where tryptophan can then bind or interact with Enzyme 1 here, could interact with Enzyme 1, let me do it in a color you can see. Could interact with Enzyme 1 so that it can no longer act as efficiently taking Precursor 1 to Precursor 2. So this right over here, this is the classic feedback inhibition, feedback inhibition. The focus of this video, we're talking about operons and gene regulation, but it's important to realize that the regulation of the creation of tryptophan doesn't only occur at the transcription level and I'm not gonna go into this video, it's a slightly more advanced topic, but there's also regulation of tryptophan biases through a process called attenuation, which doesn't affect the start of transcription, but it affects how things get completed, and it will keep tryptophan from being completely, or the entire process from going to completion. But the ones that are most typically talked about are what we just talked about here, where you have your tryptophan act as a co-repressor of the Trp repressor, and also the feedback inhibition, which once again, it's not really about gene regulation, but you can see how the product of this process can go back and inhibit one of the first enzymes.