Tryptophanase (TnaA) (TnaA)

Bacterial tryptophanase is a pyridoxal 5'-phosphate (PLP)-dependent enzyme primarily expressed by commensal bacteria in the human gut, such as Escherichia coli and Proteus vulgaris (UniProt P0A853). It catalyzes the hydrolytic cleavage of L-tryptophan into indole, pyruvate, and ammonia. While indole is a vital signaling molecule for bacterial quorum sensing and biofilm formation, it is also a precursor to indoxyl sulfate, a significant uremic toxin in humans (PubMed: 27630114). In patients with chronic kidney disease (CKD), the accumulation of indoxyl sulfate contributes to renal fibrosis, cardiovascular damage, and systemic inflammation. Because this enzyme is not present in human cells, it is considered a promising therapeutic target for reducing the production of gut-derived toxins without interfering with host metabolism. Experimental small-molecule inhibitors are being developed to lower systemic indoxyl sulfate levels and slow the progression of renal failure (PubMed: 32669573).

Other names

L-tryptophan indole-lyaseTryptophan indole-lyaseTnaAL-tryptophanase

Inhibition of the pyridoxal 5'-phosphate (PLP)-dependent catalytic activity of tryptophanase, preventing the conversion of L-tryptophan to indole, pyruvate, and ammonia.