Tryptophan indole-lyase (TIL)

Tryptophan indole-lyase is a **bacterial, pyridoxal 5'-phosphate (PLP)-dependent enzyme** (EC 4.1.99.1) that catalyzes the reversible β-elimination of indole from L-tryptophan, producing indole, pyruvate, and ammonia. It is found widely in Gram-negative bacteria such as *Escherichia coli*, *Proteus vulgaris*, and others, both in commensal gut microbiota and pathogenic strains[1][3][7][8]. The enzyme is a homotetramer, with catalytic activity requiring the PLP cofactor and stabilization by potassium ions[8][9]. Tryptophan indole-lyase plays a central role in bacterial tryptophan and nitrogen metabolism; its product, **indole**, has diverse effects on bacterial physiology, including biofilm formation, antibiotic resistance, plasmid retention, and virulence. In humans, it has gained interest as a potential drug target due to its role in the production of uremic toxins relevant to chronic kidney disease[1]. Tryptophan indole-lyase is structurally and mechanistically distinct from mammalian enzymes, with several characterized inhibitors that disrupt the enzyme by binding to the substrate or PLP sites[3][10]. There is no evidence to date that this enzyme is explicitly targeted by clinically approved drugs, but its inhibition in microbiome modulation or infection control is under investigation[1][3].

Other names

L-tryptophanaseTryptophanaseL-tryptophan indole-lyase (deaminating)TNaseTrpase

Inhibitors block the enzyme's β-elimination of indole from L-tryptophan by stabilizing reaction intermediates or binding to the PLP cofactor site[1][3][8]. PLP analogs or active site binders disrupt or prevent catalysis