The alarming spread of multidrug resistance is due to a very limited number of pathways for existing antibiotics. Biotin biosynthesis is an antimicrobial development prospect because it is essential for all life. But the synthetic pathway of Biotin is only by microorganisms and plants. There has been rising concern in the discovery of novel antibacterials. Characterizing the MOA of biologically active small molecules remains one of the biggest hurdles of whole-cell based screening in bacteria. Antibacterial compounds identify from a high-throughput screen of growth inhibition of E. coli under nutrient limitation. E. coli is a facultatively anaerobic, am-negative, coliform bacterium. The late steps of biotin synthesis are catalyzed by the enzymes BioF, BioA, BioD, BioB. BioA, also named 7,8-diaminopelargonic acid synthase, is a PLP-containing transaminase. Besides, BioA uses S-adenosylmethionine (SAM) as an unusual amino donor to convert KAPA into DAPA. MAC13772 is an enzyme BioA inhibitor with antibacterial Activity.

MAC13772 is uniquely suppressed by biotin the antepenultimate step in biotin biosynthesis in E. coli. And MAC13772 inhibits the enzyme BioA with an IC50 of 250 nM. MAC13772  inhibits BioA by the interaction of the hydrazine moiety with PLP in the active site of the enzyme. MAC13772  can serve as specific chemical probes. Furthermore, studying metabolic pathways in bacteria at a systems-level by using MAC13772. Specifically, MAC13772 is as potential leads for antibiotic drug discovery and inhibits biotin biosynthesis in E. coli. All in all, MAC13772 is a potent enzyme BioA inhibitor and has good antibacterial activity. In addition, the activity of MAC13772 is strictly dependent on biotin restriction.


 Zlitni S, et al. Nat Chem Biol. 2013 Dec; 9 (12): 796-804.