Tryptophan Operon

Introduction image

Tryptophan operon is found within the genome of E.coli that carries a set of genes for the construction of an essential amino acid tryptophan. Sometimes, it also termed as trp operon. Unlike lac or lactose operon, trp operon is a kind of repressible system that we will discuss in this article.

A scientist named Charles Yanofsky and co-workers has explicitly studied the role of regulatory and structural gene of the trp operon. Trp operon aids biosynthesis of the amino acid tryptophan from a precursor molecule “chorismic acid”.

Tryptophan functions as an effector molecule that is required for the building up the polypeptide chain. Thus, the tryptophan is the end product of the biosynthetic pathway, whose combination or dissociation with the repressor protein can turn on or turn off the trp operon system.

Content: Tryptophan Operon

  1. Definition
  2. Structure
  3. Regulation
  4. Conclusion


Trp operon can define as a repressible system, which regulates the gene expression for the biosynthesis of tryptophan according to the binding or uncoupling of a repressor with the operator region. The association and dissociation of the repressor protein strongly depend upon the tryptophan level in the surrounding.

High level of tryptophan or effector molecule escalates the binding affinity of a repressor protein with the operator sequence, which in turn terminates the gene transcription. In contrast, a low level of tryptophan results in detachment of the repressor from the operator region and allows gene expression.

Structure of Tryptophan Operon

The trp operon consists of:

structure of tryptophan operon

  • Promoter (P) region
  • Operator (O) region
  • Regulatory region
  • Attenuator (A) region
  • Structural genes (Trp A-E)

Promoter Gene

It is the region on a bacterial chromosome that comprises a specific nucleotide sequence, where an RNA polymerase can specifically bind to initiate transcription. The binding of a repressor protein with the operator inhibits the binding of RNA polymerase with the promoter sequence, which in turn terminates the transcription.

Operator Gene

It is the specific nucleotide sequence on chromosomal DNA of E.coli, where a repressor protein can bind by the association of an effector molecule or tryptophan. Here, the tryptophan molecule works as a corepressor that aids activation of aporepressor protein.

Regulatory Gene

Tryptophan operon is a repressor system, in which a regulatory gene of chromosome encodes trp repressor protein that recognizes the operator sequence. The repressor protein switch on the operon system at low trp level in the surrounding, while switching off the system at high trp level in the environment.

Therefore, a repressor protein is associated with the synthesis of five gene products mediated by the level of tryptophan in the surrounding. A repressor becomes active or inactive by the presence or absence of corepressor or effector molecule (tryptophan).

Attenuator Region

It is found in the middle of operator region and structural genes. Attenuator region comprises leader sequences (160bp in size) that regulate the transcription via attenuation.

Its mechanism is to attenuate the efficiency of transcription at sufficient tryptophan inside the bacterial cell by the formation of dimers. Oppositely, the RNAp can traverse through the attenuator region and can transcribe the genes necessary for trp construction, at low tryptophan level.

Structural Genes

In tryptophan operon, there are five structural genes, namely Trp A, B, C, D and E. The structural genes encodes for the enzymes and its subunits important for the biosynthesis of tryptophan from chorismic acid.

  • trpE encodes the enzyme Anthranilate synthase I.
  • trpD encodes the enzyme Anthranilate synthase II.
  • trpC encodes the enzyme N-5’-Phosphoribosyl anthranilate isomerase and Indole-3-glycerolphosphate synthase.
  • trpB encodes the enzyme tryptophan synthase-B subunit.
  • trpA encodes the enzyme tryptophan synthase-A subunit.

Regulation of Tryptophan Operon

Two mechanisms regulate the trp operon.

  • Repressor or derepression mechanism
  • Attenuation mechanism

Repression of Tryptophan Operon

It occurs when the trp level is high in the surrounding medium. In this case, the TrpR gene of the tryptophan operon releases apo-repressor (inactive) protein that alone cannot attach to the operator region.

But, in the presence of corepressor or tryptophan the apo-repressor protein activates and blocks the RNA polymerase to initiate the transcription or inhibits the enzymes necessary for the trp construction. Therefore, the respective RNA polymerase can neither bind with the operator gene, nor it can transcribe the structural genes, at high tryptophan concentration.

repression of tryptophan operon

Expression of trp operon during availability of tryptophan simply means that the operon system will switch off to terminate the transcription. Hence, the repression of trp operon is mediated via complex formed by the association of an allosteric repressor and an effector molecule.

Tryptophan functions as a corepressor or an effector molecule that transforms the inactive apo-repressor to an active repressor, which then adheres to the operator sequence to block gene expression.

Derepression of Tryptophan Operon

It occurs in the case of low tryptophan level in the environment. The active repressor protein attached to the operator region will detach, due to lack of sufficient effector molecule. After its dissociation, the repressor remains inactive and functionless. As a result, RNA polymerase becomes free to further transcribe the structural genes for the synthesis of tryptophan.

derepression of tryptophan operon

The expression of trp operon during unavailability of tryptophan simply means that the operon system will switch on for the transcription of structural genes by the RNA polymerase. Hence, the derepression is achieved by the dissociation of repressor protein due to lack of trp or effector molecules, which together can form an active complex.


It is the second regulatory region of the trp operon controlled by the trpL gene, also called attenuator. A leader sequence controls the gene expression via a mechanism called attenuation and comprises a polypeptide sequence plus an attenuator (contains palindromic sequences).

Attenuator region in trp operon

Once the bacterial DNA is transcribed into mRNA, the attenuator sequence can form dimers via the pairing of palindromic sequences. There are four domains in the leader sequence, in which domain-3 can pair with either domain-2 or domain-4, and domain-1 can pair with domain-2 and comprises two trp residues.

The pairing of domain-2 and 3 results antitermination, while the pairing of domain-3 and 4 causes a termination of trp biosynthesis. The presence of domain-4 (also called attenuator) is important to terminate the transcription, because it only can facilitate stem-loop formation. The mechanism of attenuation depends upon pairing of the ribosome and the level of tryptophan inside the bacterial cell.

At low tryptophan level

The ribosome sits at the domain-1 of the mRNA transcript and translates it very slowly due to low tryptophan level. As a result, domain-3 interacts with domain-2 due to the halt of the ribosome at domain-1. In such a case, the stem and loop structure will not form by which the transcription may continue to synthesize the enzymes necessary for trp production.

attenuation of trp operon at low trp level

At high tryptophan level

The ribosome rapidly translates the domain-1 and sits at the domain-2, when the concentration of tryptophan is high inside the cell. As a result, domain-3 associates with domain-4 and aids the formation of hair-loop structure.

attenuation of trp operon at high trp level

The dimerization of domain-3 and 4 cause the RNAp to fall off, and the prevents mRNA to further transcribe the gene encoding enzymes for the trp biosynthesis. Therefore, the attenuator functions as a barrier at high trp concentration by the pairing of self-complementary sequences.


Therefore, we can conclude that the tryptophan repressor and attenuation system decides when to switch on or switch off the expression of the gene for trp synthesis, according to the availability of tryptophan.

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