Dihydrofolate reductase (Escherichia coli) (eDHFR)

Dihydrofolate reductase from Escherichia coli (eDHFR) is a vital enzyme in the bacterial folate biosynthetic pathway, responsible for the NADPH-dependent reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate (UniProt: P0ABQ4). Tetrahydrofolate serves as an essential one-carbon donor for the synthesis of thymidylate, purines, and several amino acids, making eDHFR indispensable for DNA replication and bacterial growth (PubMed: 9214328). Because of its central metabolic role, eDHFR is a primary target for antibiotics such as trimethoprim, which exhibits high affinity for the bacterial enzyme while sparing the human version (DrugBank: DB00440). Beyond its role in infectious disease, eDHFR is widely employed in synthetic biology as a chemical-genetic tool; specifically, destabilized mutants of eDHFR serve as 'degrons' that can be stabilized by the addition of trimethoprim, allowing for precise temporal control of protein function (PubMed: 20811468). Clinical challenges associated with eDHFR include the rapid emergence of resistance through point mutations in the folA gene or the acquisition of bypass enzymes via horizontal gene transfer (PubMed: 29439114).

Other names

folADHFRE. coli DHFRDihydrofolate reductase

Competitive inhibition of the enzyme dihydrofolate reductase, which blocks the reduction of dihydrofolate to tetrahydrofolate, thereby halting the synthesis of essential nucleic acids and proteins in bacteria.