The trp operon is a group of genes in bacteria encoding enzymes for tryptophan biosynthesis that is coordinately regulated by intracellular tryptophan levels.
Explanation
In the bacterium Escherichia coli and related species, five structural genes (trpE, trpD, trpC, trpB and trpA) encode enzymes that convert chorismate into the amino acid tryptophan. Upstream of these genes lie a promoter, operator and leader sequence. The operon is controlled by a regulatory protein encoded by the trpR gene elsewhere on the chromosome. When intracellular tryptophan concentrations are low, the Trp repressor is inactive and cannot bind the operator; RNA polymerase binds the promoter and transcribes the operon, producing a single polycistronic mRNA that is translated into all five enzymes. As tryptophan levels rise, tryptophan molecules act as corepressors, binding to the Trp repressor and inducing a conformational change that allows it to bind the operator and block transcription. A second layer of control, attenuation, relies on a leader peptide containing tandem tryptophan codons. When tryptophan is scarce, ribosomes stall at the leader peptide and allow an antiterminator hairpin in the mRNA to form, enabling transcription of the downstream genes. When tryptophan is abundant, rapid translation of the leader peptide allows formation of a terminator hairpin that causes premature termination of transcription. This dual regulatory scheme allows the operon to fine‑tune expression across a range of tryptophan concentrations.
Notable features and examples
The trp operon is a classic example of a repressible operon and negative feedback in prokaryotic gene regulation. Mutations in the trpR gene or operator sequence that prevent repressor binding result in constitutive expression of tryptophan biosynthetic enzymes. Conversely, mutations in the promoter can reduce transcription regardless of tryptophan levels. Laboratory experiments often use the trp operon to illustrate attenuation by replacing the leader peptide with reporter genes. Some other bacteria, such as Bacillus subtilis, also regulate tryptophan biosynthesis via attenuation, though the mechanism uses a small RNA rather than a leader peptide. Synthetic biologists have harnessed trp operon components to build inducible expression systems responsive to tryptophan or analogues.
The trp operon demonstrates how bacteria coordinate metabolic pathways with nutrient availability. Its layered control via repression and attenuation provides a paradigm for understanding transcriptional regulation in prokaryotes.
Related Terms: Operon, Repressor, Attenuation, Tryptophan, Gene regulation