- [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.