Adenosylmethionine-8-amino-7-oxononanoate aminotransferase (BioA) (BioA)

Adenosylmethionine-8-amino-7-oxononanoate aminotransferase (BioA) is a pyridoxal 5'-phosphate (PLP)-dependent enzyme essential for the survival of Mycobacterium tuberculosis (Mtb). It catalyzes the second step of the biotin biosynthesis pathway, converting 7-keto-8-aminopelargonic acid (KAPA) into 7,8-diaminopelargonic acid (DAPA) (UniProt P9WNR3). Because humans lack the enzymes to synthesize biotin and must obtain it from dietary sources, BioA is considered an attractive target for the development of narrow-spectrum antibiotics with minimal host toxicity (PubMed: 21214243). Inhibition of BioA results in biotin starvation, which impairs the function of biotin-dependent carboxylases required for fatty acid synthesis and energy metabolism in the pathogen (PubMed: 25191843). Research has identified several classes of inhibitors, including the natural product amiclenomycin and various synthetic small molecules like aryl hydrazines, which act by forming covalent or tight-binding complexes with the PLP cofactor (PubMed: 21903598). Targeting BioA is particularly relevant for treating multi-drug resistant tuberculosis (MDR-TB) and latent infections where the bacterium remains metabolically active but non-replicating.

Other names

7,8-diaminopelargonic acid synthaseDAPA synthaseKAPA aminotransferaseBIOA_MYCTU

Inhibition of the transamination reaction that converts 7-keto-8-aminopelargonic acid (KAPA) to 7,8-diaminopelargonic acid (DAPA), leading to biotin depletion and bacterial death.