Cytosine deaminase (non-human) (CDA)

Cytosine deaminase (abbreviated CDA) is a non-human (microbial or fungal) enzyme that catalyzes the deamination of cytosine to uracil and, critically for therapeutic applications, converts the antifungal prodrug 5-fluorocytosine into the cytotoxic agent 5-fluorouracil[2]. The enzyme is absent in mammalian cells, which allows it to be used selectively in gene-directed enzyme prodrug therapy for cancer, where delivery of the CDA gene to tumor cells enables local conversion of systemically administered 5-fluorocytosine to chemotherapeutically active 5-fluorouracil within the tumor environment. Structurally, CDA forms a dimer or tetramer and features a conserved zinc-dependent active site[2]. Two major phylogenetic clades exist for CDA: one in bacteria and another in fungi, with about 35% amino acid identity between them[2]. CDA is not an endogenous human therapeutic target, but its unique microbial presence and role in activating a prodrug for clinical use makes it an important exogenous therapeutic enzyme in oncology and antifungal therapy[2].

Other names

Cytosine aminohydrolasenon-mammalian cytosine deaminasemicrobial cytosine deaminase

Catalyzes hydrolytic deamination of cytosine and 5-fluorocytosine, converting cytosine to uracil and 5-fluorocytosine to 5-fluorouracil, which inhibits nucleic acid synthesis and is toxic to dividing cells[2]