Flavin mononucleotide-dependent oxidoreductase (FMN-OR)

FMN-dependent oxidoreductases are a diverse superfamily of enzymes that utilize flavin mononucleotide (FMN) as a non-covalently or covalently bound cofactor to facilitate a wide range of redox reactions (UniProt Consortium, 2023). These enzymes are characterized by their ability to perform one- or two-electron transfers, making them essential components of metabolic pathways, detoxification processes, and cellular signaling across all domains of life (Williams & Bruce, 2002). In clinical pharmacology, they are most notable for their role in the bioactivation of nitro-containing prodrugs; for instance, bacterial nitroreductases convert antibiotics such as nitrofurantoin and metronidazole into reactive, cytotoxic intermediates that damage microbial DNA (Roldán et al., 2008). In humans, the NADPH-cytochrome P450 reductase (POR) is a critical FMN-dependent enzyme that serves as the primary electron donor for all microsomal cytochrome P450 enzymes, thereby governing the metabolism of numerous drugs and the biosynthesis of steroid hormones (Pandey & Flück, 2013). Due to their central role in drug metabolism and their potential for selective prodrug activation, these enzymes are significant targets in both antimicrobial therapy and oncology, particularly in gene-directed enzyme prodrug therapy (GDEPT) (Valiauga et al., 2018).

Other names

FMN-binding oxidoreductaseFMN-dependent flavoproteinNitroreductase familyOld Yellow Enzyme familyFlavoenzyme

Reductive bioactivation of prodrugs into cytotoxic species and electron transfer to partner enzymes such as Cytochrome P450.