Bacterial thymidylate synthase and DNA polymerase (TS / DNA Pol)

Bacterial thymidylate synthase and DNA polymerase are essential enzymes that coordinate the synthesis and assembly of DNA in bacterial cells. Thymidylate synthase (TS) is responsible for the de novo production of deoxythymidine monophosphate (dTMP), which is a critical precursor for DNA synthesis (PubMed: 15590570). DNA polymerase, specifically the replicative Pol III complex in bacteria, then incorporates these nucleotides into the growing DNA strand during replication (PubMed: 22414679). Because these enzymes are vital for genomic integrity and cellular proliferation, they serve as important targets for antimicrobial therapy. Inhibition of thymidylate synthase leads to a depletion of thymine nucleotides, resulting in thymineless death, a phenomenon where cells undergo rapid DNA fragmentation (PubMed: 21112367). DNA polymerase inhibitors directly halt the replication fork, preventing bacterial division. While many inhibitors of these enzymes are used in cancer therapy, research continues into bacterial-specific inhibitors to treat resistant infections while minimizing toxicity to human host cells (PubMed: 16157244).

Other names

Thymidylate synthetaseDNA-directed DNA polymerasethyAdnaEpolCpolA

Inhibition of dTMP synthesis and DNA strand elongation