- [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.
