Bacterial flavoenzyme

Bacterial flavoenzymes are a diverse group of proteins that utilize flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN) as essential cofactors to catalyze a wide range of redox reactions (Joosten & van Berkel, 2007, https://doi.org/10.1016/j.cbpa.2007.01.010). These enzymes play critical roles in bacterial metabolism, including the respiratory chain, fatty acid oxidation, and the biosynthesis of essential nutrients (Massey, 2000, https://doi.org/10.1042/bst0280283). In the context of pharmacology, they are significant because several clinical antibiotics, such as nitrofurantoin and metronidazole, act as prodrugs that are specifically activated by bacterial flavoenzymes, such as oxygen-insensitive nitroreductases, into toxic reactive species that damage bacterial DNA and proteins (Williams et al., 2015, https://doi.org/10.1099/mic.0.000011). Furthermore, because certain bacterial flavoenzymes have unique structural features or metabolic roles not found in humans, they are being actively explored as targets for novel narrow-spectrum antimicrobial agents (Macheroux et al., 2011, https://doi.org/10.1111/j.1742-4658.2011.08060.x). However, the high degree of conservation in some flavin-binding sites poses a challenge for achieving selectivity over human mitochondrial flavoenzymes (Walsh & Wencewicz, 2016, Antibiotics: Challenges, Mechanisms, Opportunities).

Other names

Bacterial flavoproteinFMN-dependent enzymeFAD-dependent enzymeFlavin-containing enzymeBacterial nitroreductase

Reductive bioactivation of prodrugs into reactive radicals; Competitive inhibition of flavin cofactor binding; Covalent modification of the flavin prosthetic group.