Biotin is an enzymatic cofactor involved in amino acid metabolism, gluconeogenesis, and fatty acid synthesis. Bacteria such as E. coli, M. tuberculosis, and B. subtilis have the biosynthetic machinery to produce biotin, while humans must acquire this in their diet. As such, enzymes involved in biotin synthesis are attractive targets to induce bacteriostatic effects. 7,8-Diaminopelargonic acid synthase (BioA) is a transaminase in the biotin synthetic pathway. Kinetic studies reveal that unlike other bacteria, B. subtilis requires a lysine amino donor for KAPA transamination. Incorporation of the 15N-labeled ε-amine was detected by measuring the formation of isotopically-labeled biotin by an LC-ESI-MS method. We report the first crystal structure of B. subtilis BioA with bound substrate-lysine. Binding was attributed to a narrow binding pocket, pervading van der waals interactions, and an electrostatic interaction between the lysine carboxylate group and Arg410.

Transamination of 7-keto-8-aminopelargonic acid (KAPA) with amino-donor lysine in Bacillus subtilis

255th National Meeting (2018)

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