Tryptophan synthase beta subunit (TrpB)

Tryptophan synthase beta subunit (TrpB) is a pyridoxal 5-phosphate (PLP)-dependent enzyme that catalyzes the final step of L-tryptophan biosynthesis (UniProt: P9WFY1). It typically functions as part of an alpha2-beta2 tetrameric complex where it condenses indole, channeled from the alpha subunit, with L-serine to produce tryptophan (PubMed: 26148440). Because the tryptophan biosynthetic pathway is essential for many bacteria and fungi but is entirely absent in humans, TrpB is a highly attractive target for the development of narrow-spectrum antimicrobial agents (PubMed: 29335258). Specifically, it has been identified as a vulnerable metabolic node in Mycobacterium tuberculosis, where its inhibition leads to tryptophan starvation and subsequent bacterial death (PubMed: 24003076). Experimental small-molecule inhibitors like BRD4592 have demonstrated the feasibility of targeting this enzyme to treat infections without affecting human host cells (PubMed: 27631095). However, therapeutic development must consider the potential impact on the commensal gut microbiota, which also utilizes this biosynthetic pathway.

Other names

Tryptophan synthase subunit betaL-tryptophan synthetaseTrpBTSB

Inhibition of the pyridoxal phosphate-dependent condensation of indole and L-serine to form L-tryptophan, leading to amino acid starvation in the pathogen (PubMed: 27631095).