Cytosine deaminase (bCD) (bCD)

Bacterial cytosine deaminase (bCD) is an enzyme primarily found in bacteria and fungi, such as Escherichia coli, that catalyzes the hydrolytic deamination of cytosine to uracil (UniProt: P0A6B4). Because mammalian cells lack this enzyme, it is extensively utilized in Gene-Directed Enzyme Prodrug Therapy (GDEPT) for cancer treatment (PubMed: 25650541). In this approach, the bCD gene is delivered to tumor cells, where it converts the non-toxic prodrug 5-fluorocytosine (5-FC) into the potent cytotoxic agent 5-fluorouracil (5-FU) (PubMed: 11033172). This localized production of 5-FU allows for high therapeutic concentrations within the tumor while minimizing systemic toxicity. The treatment's effectiveness is often enhanced by the bystander effect, where 5-FU diffuses to neighboring untransduced cells, expanding the zone of cell death (PubMed: 15611114). Beyond oncology, the enzyme is a target for antifungal agents like 5-FC, which selectively inhibits fungal growth by exploiting the presence of CD in pathogens but not in the human host (PubMed: 12165235). However, challenges remain, including the potential immunogenicity of the bacterial protein and the unintended conversion of prodrugs by commensal gut microbiota.

Other names

Cytosine aminohydrolasecodAEscherichia coli cytosine deaminasebCDABacterial CD

The enzyme catalyzes the hydrolytic deamination of the prodrug 5-fluorocytosine (5-FC) into 5-fluorouracil (5-FU). 5-FU is subsequently converted by host cellular enzymes into metabolites that inhibit thymidylate synthase and incorporate into RNA and DNA, leading to cell cycle arrest and apoptosis.