Trehalose-6-phosphate synthase (TPS)

Trehalose-6-phosphate synthase (TPS) is the primary enzyme responsible for the first step of trehalose biosynthesis, catalyzing the conversion of UDP-glucose and glucose-6-phosphate into trehalose-6-phosphate (UniProt: P32327). This enzyme is essential in various organisms, including bacteria, fungi, and plants, where trehalose acts as a critical stress protectant and structural component (PMID: 30256119). In human pathogens like Mycobacterium tuberculosis and Candida albicans, TPS is vital for maintaining cell wall integrity and virulence, yet it is entirely absent in the human genome (PMID: 28653490). This absence makes TPS an attractive target for the development of highly selective antifungal and antibacterial agents with minimal off-target effects in humans. While no TPS inhibitors are currently approved for clinical use, compounds like Validamycin A have demonstrated the potential of targeting this pathway in agricultural and laboratory settings. Research is ongoing to identify potent small-molecule inhibitors that can penetrate the complex cell walls of pathogens to disrupt their metabolic stability. Beyond infectious diseases, TPS is also a target in agricultural biotechnology to improve crop resilience to drought and temperature extremes.

Other names

Alpha,alpha-trehalose-6-phosphate synthase (UDP-forming)UDP-glucose-glucose-6-phosphate glucosyltransferaseTPS1TPSATPSBOtsATrehalose-6-phosphate synthetase

Competitive inhibition of the enzyme's active site, preventing the synthesis of trehalose-6-phosphate and disrupting downstream metabolic and structural processes in pathogens.