Fungal thymidylate synthase (TS)

Thymidylate synthase is an essential enzyme that catalyzes the conversion of deoxyuridine monophosphate (dUMP) to deoxythymidine monophosphate (dTMP), a critical step in the de novo biosynthesis pathway for pyrimidine nucleotides required for DNA replication and repair. The reaction uses 5,10-methylenetetrahydrofolate as a methyl donor and produces dihydrofolate as a byproduct. In fungi—as in other eukaryotes—this enzyme is indispensable for both nuclear and mitochondrial DNA synthesis. Because its activity is vital for cell proliferation, it represents an attractive therapeutic target; inhibition leads to nucleotide imbalance and ultimately cell death due to impaired DNA synthesis ("thymineless death"). While most research has focused on human or bacterial enzymes, fungal thymidylate synthase shares conserved catalytic mechanisms but may have unique structural features exploitable by selective antifungal agents[1][6].

Other names

Thymidylate synthaseTSThyA (for classical type)Thymidylate synthetase

*For drugs targeting this enzyme class generally:* - Inhibition of dUMP methylation to dTMP, leading to depletion of dTTP pools and inhibition of DNA synthesis[1][3] *Inhibitors may act as substrate analogs or bind the folate cofactor site.*