TrpA

trpA is a gene found in many bacteria that encodes the alpha subunit of tryptophan synthase, an enzyme essential for de novo synthesis of the amino acid tryptophan. The TrpA protein forms, together with the beta subunit TrpB, the active holoenzyme tryptophan synthase α2β2, which operates in the final steps of tryptophan biosynthesis.

Function and mechanism: The TrpA subunit catalyzes the cleavage of indole-3-glycerol phosphate (IGP) to produce indole and glyceraldehyde-3-phosphate. The indole is subsequently transferred to TrpB, which catalyzes the condensation of indole with serine to form tryptophan. The two subunits work in close proximity within the holoenzyme, enabling substrate channeling that increases catalytic efficiency and minimizes diffusion of the reactive indole intermediate.

Genetic and regulatory context: trpA is part of the bacterial trp operon, which encodes enzymes involved in tryptophan biosynthesis. Expression is tightly regulated by the TrpR repressor, which binds tryptophan and the operator to repress transcription when tryptophan is plentiful. Attenuation mechanisms linked to tryptophan availability provide additional control of operon transcription in many organisms.

Variation and significance: The trpA gene is widely conserved among bacteria, with the encoded alpha subunits typically around 260 amino acids in length. Mutations in trpA can disrupt tryptophan production, resulting in auxotrophy unless tryptophan is supplied externally. Studied extensively in model organisms such as Escherichia coli, trpA contributes to understanding of operon regulation and enzyme complex assembly in amino acid biosynthesis.