8-amino-7-oxononanoate synthase (AONS)

8-amino-7-oxononanoate synthase (AONS), also known as BioF, is a pyridoxal 5'-phosphate (PLP)-dependent enzyme that catalyzes the first committed step of de novo biotin (vitamin B7) biosynthesis in bacteria, fungi, and plants [2, 3]. It facilitates the decarboxylative condensation of L-alanine and a pimeloyl-thioester (such as pimeloyl-CoA or pimeloyl-acyl carrier protein) to produce 8-amino-7-oxononanoate, a critical intermediate in the assembly of the biotin ring [4, 5, 10]. This metabolic pathway is essential for the survival of several major human pathogens, including Mycobacterium tuberculosis, making AONS a promising target for the development of selective antimicrobial agents [4, 6]. Because humans lack the enzymes for de novo biotin synthesis and must obtain the vitamin from dietary sources, targeting AONS offers a mechanism for selective toxicity with minimal risk of host interference [10]. Inhibition of AONS results in the depletion of biotin, which serves as a vital cofactor for carboxylases involved in fatty acid synthesis and energy metabolism, eventually leading to microbial growth arrest [11]. While there are currently no AONS-targeted drugs in clinical use, research efforts continue to explore suicide inhibitors and transition-state analogs as potential therapeutic leads [7, 8].

Other names

7-keto-8-aminopelargonic acid synthaseKAPA synthase7-KAP synthase8-amino-7-oxopelargonate synthaseBioF7-keto-8-aminopelargonate synthase

Inhibition of the biotin biosynthetic pathway by blocking the condensation of L-alanine and pimeloyl-CoA, leading to the depletion of essential metabolic cofactors and resulting in bacterial or fungal growth arrest.