FAD synthase (FMN adenylyltransferase) (FADS)

FAD synthase (FMN adenylyltransferase) is a critical enzyme that catalyzes the final step of flavin adenine dinucleotide (FAD) biosynthesis by transferring an adenylyl group from ATP to flavin mononucleotide (FMN) (UniProt Q8NFF5). In humans, it is encoded by the FLAD1 gene and exists in multiple isoforms localized to the cytosol and mitochondria, where it maintains the pool of FAD cofactors required for the activity of numerous flavoproteins involved in the electron transport chain and fatty acid beta-oxidation (GeneCards FLAD1). Mutations in FLAD1 lead to FAD synthase deficiency, a rare metabolic disorder characterized by multiple acyl-CoA dehydrogenase deficiency (MADD) and combined respiratory chain dysfunction, manifesting as neuromuscular weakness, exercise intolerance, or severe neonatal distress (PMID: 27259049). Therapeutic management typically involves high-dose riboflavin supplementation, which can act as a molecular chaperone to stabilize the enzyme or as a substrate to enhance residual catalytic activity (PMID: 27259049). Furthermore, the enzyme is considered a promising target for novel antibacterial agents because bacterial FAD synthases are structurally distinct from their human counterparts, allowing for the potential development of species-specific inhibitors (PMID: 28840747).

Other names

FMN adenylyltransferaseFAD pyrophosphorylaseFAD-adenylyl transferaseFlavin adenine dinucleotide synthetase 1PP591FAD1LSMFLAD

Drugs targeting FAD synthase primarily act through substrate supplementation or molecular chaperoning using riboflavin to stabilize mutant enzyme forms and restore cellular FAD levels in patients with FLAD1 deficiency (PMID: 27259049). In the context of antimicrobial development, experimental inhibitors aim to competitively or non-competitively block the enzyme's active site, disrupting essential flavin-dependent metabolic pathways in pathogens (PMID: 28840747).