Dethiobiotin synthetase (DTBS) (DTBS)

Dethiobiotin synthetase (DTBS), also known as BioD, is a critical enzyme in the de novo biosynthesis of biotin (vitamin B7), a vital cofactor for metabolic processes such as fatty acid synthesis and gluconeogenesis [1, 6, 7]. It catalyzes the penultimate step of the pathway, specifically the ATP-dependent conversion of 7,8-diaminononanoic acid (DAPA) and carbon dioxide into dethiobiotin through the formation of a ureido ring [2, 6, 11]. This enzyme is found in bacteria, fungi, and plants but is absent in mammals, who must obtain biotin from their diet [3, 6, 12]. Consequently, DTBS is a highly attractive target for the development of novel antimicrobial agents, particularly against Mycobacterium tuberculosis, where biotin synthesis is essential for survival and virulence [3, 12]. Current drug discovery efforts focus on small-molecule inhibitors, such as substrate analogs and transition-state mimics like tetrazole 7a, that disrupt the enzyme's activity to halt microbial growth [3, 6]. However, a potential challenge for DTBS-targeted therapies is the ability of some pathogens to scavenge biotin from the host environment, which may limit the efficacy of these inhibitors in certain clinical contexts [6, 12].

Other names

BioDDethiobiotin synthase7,8-diaminononanoate carbamoyltransferaseDTB synthetase7,8-diaminononanoate:carbon-dioxide cyclo-ligase (ADP-forming)

Inhibition of the biotin biosynthetic pathway by preventing the conversion of 7,8-diaminononanoic acid to dethiobiotin, thereby depleting the essential cofactor biotin and inhibiting microbial growth.