Escherichia coli dihydrofolate reductase (EcDHFR)

Escherichia coli dihydrofolate reductase (EcDHFR) is a 159-amino acid enzyme that catalyzes the reduction of 7,8-dihydrofolate to 5,6,7,8-tetrahydrofolate using NADPH as a cofactor (UniProt: P0ABQ4). This reaction is a critical step in the folate cycle, providing the one-carbon units necessary for the biosynthesis of thymidylate, purines, and amino acids like methionine (PubMed: 10403544). As a therapeutic target, EcDHFR is the primary site of action for the antibiotic trimethoprim, which binds the enzyme with significantly higher affinity than it does human DHFR, thereby selectively inhibiting bacterial growth (PubChem: CID 2520). The specific mention of 'fusion monomers' often refers to the use of EcDHFR in protein-fragment complementation assays (PCA), where the enzyme is split into domains and fused to other proteins to monitor protein-protein interactions in vivo (PubMed: 9561210). Mutations in the folA gene, which encodes EcDHFR, are a major cause of clinical resistance to trimethoprim in E. coli infections (PubMed: 15694505). Overall, EcDHFR remains a cornerstone of both antimicrobial pharmacology and synthetic biology research.

Other names

DHFRfolADihydrofolate reductase5,6,7,8-tetrahydrofolate:NADP+ oxidoreductase

Competitive inhibition of the enzyme dihydrofolate reductase, preventing the reduction of dihydrofolate to tetrahydrofolate, which halts the synthesis of precursors required for DNA and RNA production.