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

Adenosylmethionine-8-amino-7-oxononanoate aminotransferase, commonly known as BioA, is a pyridoxal phosphate (PLP)-dependent enzyme essential for the de novo biosynthesis of biotin (vitamin B7) in various bacteria, including Mycobacterium tuberculosis (UniProt P9WNS3). It catalyzes the transamination of 7-keto-8-aminopelargonic acid (KAPA) to 7,8-diaminopelargonic acid (DAPA), using S-adenosyl-L-methionine as the amino donor (PubMed: 21105715). Because humans lack the biotin biosynthetic pathway and must acquire the vitamin through their diet, BioA represents a highly attractive and selective target for the development of novel antibiotics (PubMed: 20812715). Inhibition of BioA leads to biotin starvation, which disrupts essential metabolic processes such as fatty acid synthesis and gluconeogenesis, ultimately resulting in the cessation of bacterial growth (PubMed: 25607115). Research has identified several potent inhibitors, including the natural product amiclenomycin and various synthetic small molecules like MAC13772, which demonstrate efficacy against both active and latent stages of tuberculosis (PubMed: 22409548). The enzyme's unique substrate specificity and the absence of a human ortholog minimize the risk of host toxicity, though potential interference with other human PLP-dependent enzymes remains a consideration in drug design (PubMed: 21105715).

Other names

7,8-diaminopelargonic acid synthaseDAPA synthase8-amino-7-oxononanoate transaminaseBioA protein

Inhibition of biotin biosynthesis by blocking the conversion of 7-keto-8-aminopelargonic acid (KAPA) to 7,8-diaminopelargonic acid (DAPA), leading to bacterial growth arrest (PubMed: 21105715).