Enzymes in riboflavin biosynthesis: Potential antibiotic drug targets

The rapid resistance of pathogens to antibiotics has emerged as a major threat to global health. Identification of new antibiotic targets is thus needed for developing alternative drugs. Genes encoding enzymes involved in the biosynthesis of riboflavin and flavin cofactors (FMN/FAD) are attractive targets because these enzymatic reactions are necessary for most bacteria to synthesize flavin cofactors for use in their central metabolic reactions. Moreover, humans lack most of these enzymes because we uptake riboflavin from our diet. This review discusses the current knowledge of enzymes involved in bacterial biosynthesis of riboflavin and other flavin cofactors, as well as the functions of the FMN riboswitch. Here, we highlight recent progress in the structural and mechanistic characterization, and inhibition of GTP cyclohydrolase II (GCH II), lumazine synthase (LS), riboflavin synthase (RFS), FAD synthetase (FADS), and FMN riboswitch, which have been identified as plausible antibiotic targets. As the structures and functions of these enzymes and regulatory systems are not completely understood, they are attractive as subjects for future in-depth biochemical and biophysical analysis.