Cytosine deaminase (yCD) (yCD)

Cytosine deaminase (yCD), specifically the isoform from Saccharomyces cerevisiae encoded by the FCY1 gene, is a hydrolytic enzyme that catalyzes the conversion of cytosine to uracil (UniProt: P05016). While not naturally present in mammalian cells, it is a primary tool in Gene-Directed Enzyme Prodrug Therapy (GDEPT) for cancer treatment. In this approach, the yCD gene is delivered to tumor cells, enabling them to locally convert the non-toxic prodrug 5-fluorocytosine (5-FC) into the highly cytotoxic agent 5-fluorouracil (5-FU) (PubMed: 17110387). This localized activation aims to concentrate the chemotherapy within the tumor microenvironment, thereby reducing the systemic side effects typically associated with 5-FU. The enzyme functions as a homodimer and utilizes a zinc-dependent mechanism to facilitate the deamination at the C4 position of the pyrimidine ring (PubMed: 12590518). A significant advantage of this system is the bystander effect, where the produced 5-FU diffuses to neighboring non-transduced cells, though challenges remain regarding the potential for systemic toxicity and the host's immune response to the fungal protein (PubMed: 25650515).

Other names

FCY1Yeast cytosine deaminaseSaccharomyces cerevisiae cytosine deaminaseCDase5-FC deaminase

The enzyme catalyzes the hydrolytic deamination of the prodrug 5-fluorocytosine (5-FC) into the potent antimetabolite 5-fluorouracil (5-FU), which subsequently inhibits DNA and RNA synthesis (PubMed: 17110387).