Cytosine deaminase (Saccharomyces cerevisiae) (yCD)

Yeast cytosine deaminase (yCD) is an enzyme originating from the yeast Saccharomyces cerevisiae that plays a vital role in the pyrimidine salvage pathway by converting cytosine into uracil (UniProt: P25334). Because mammalian cells lack this specific enzyme, it has been extensively developed as a tool for Gene-Directed Enzyme Prodrug Therapy (GDEPT) in cancer treatment. In this therapeutic approach, the yCD gene is delivered to tumor cells via a vector, such as the retroviral replicating vector vocimagene amiretrorepvec (Toca 511), followed by the systemic administration of the non-toxic prodrug 5-fluorocytosine (5-FC) (PubMed: 27103014). The yCD enzyme expressed within the tumor then selectively converts 5-FC into the potent chemotherapeutic agent 5-fluorouracil (5-FU), which inhibits DNA and RNA synthesis to induce cell death. This localized production of 5-FU achieves high intratumoral drug concentrations while minimizing systemic toxicity, and it benefits from a significant bystander effect where the drug diffuses to kill neighboring non-transduced cancer cells (PubMed: 31811060).

Other names

FCY1Yeast cytosine deaminaseyCDCytosine aminohydrolaseCytosine deaminase (Saccharomyces cerevisiae)

The enzyme catalyzes the hydrolytic deamination of the non-toxic prodrug 5-fluorocytosine (5-FC) into the cytotoxic metabolite 5-fluorouracil (5-FU), which subsequently inhibits thymidylate synthase and incorporates into RNA/DNA to cause cell death (PubMed: 10449155).