the trp operon

Imagine a small factory that makes a particular part. As long as the warehouse shelf for that part is empty, the line runs. As the shelf fills up, you would want the line to slow down and eventually stop — no sense making parts you already have piled up. The trp operon is a bacterial factory for making the amino acid tryptophan, and it shuts itself down precisely when tryptophan is plentiful.

The trp operon is a cluster of five genes in E. coli encoding the enzymes that build tryptophan from a simpler precursor, all under one promoter and operator. It is a repressible system: normally on (because the cell usually needs to make tryptophan), and switched off when tryptophan accumulates. The switch works through a repressor protein that, on its own, cannot bind the operator. Tryptophan itself acts as a corepressor: when tryptophan is abundant, it binds the repressor and changes its shape so the repressor can now grip the operator and block transcription. When tryptophan is scarce, no corepressor is bound, the repressor cannot hold the DNA, and the genes stay on. So the product of the pathway controls its own production — a clean negative feedback loop built into gene regulation.

The trp operon is the textbook repressible operon, the natural counterpart to the inducible lac operon, and it illustrates feedback at the level of transcription. But its real fame comes from a second, more delicate control layered on top: attenuation, a fine-tuning mechanism that adjusts transcription according to how much tryptophan is around, by deciding whether RNA polymerase finishes the message or quits early. Repression provides the coarse on/off; attenuation provides the fine dial. A useful contrast to keep straight: in lac the small molecule (allolactose) turns the operon on, while in trp the small molecule (tryptophan) turns it off.