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Cytosine deaminase (fungal)

Molecular classification
Enzyme, Deaminase, Hydrolase, Pyrimidine metabolism enzyme
01

Overview

Cytosine deaminase (fungal) is an enzyme found in yeast and other fungi, but not in mammalian cells. It catalyzes the hydrolytic deamination of cytosine to uracil, thus playing a key role in the pyrimidine salvage pathway. Of special therapeutic relevance, it converts the prodrug 5-fluorocytosine to 5-fluorouracil, a potent cytotoxic molecule widely used in antifungal and anticancer applications. The enzyme is a zinc-dependent hydrolase, structurally distinct from its bacterial counterparts but mechanistically similar. Fungal cytosine deaminase is utilized in gene-directed enzyme prodrug therapy (GDEPT) approaches for targeted cancer treatment. Deficiency or absence of this enzyme in certain fungi confers resistance to 5-fluorocytosine. The most well-studied fungal form is encoded by the FCY1 gene in Saccharomyces cerevisiae[1][2][3][4].

Other names
Fungal cytosine deaminaseYeast cytosine deaminaseFCY1 (gene name in S. cerevisiae)
02

Mechanism of action

Catalyzes conversion of cytosine to uracil Catalyzes conversion of 5-fluorocytosine (5-FC, a prodrug) to 5-fluorouracil (5-FU, a cytotoxic agent)

03

Biological functions

Pyrimidine salvageHydrolytic deamination of cytosine to uracilConversion of 5-methylcytosine to thymineProdrug activation (conversion of 5-fluorocytosine to 5-fluorouracil)
04

Disease associations

Cancer (in the context of gene-directed enzyme prodrug therapy)Infection (implicated in antifungal resistance)
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Safety considerations

Potential off-target conversion of 5-fluorocytosine in human microbial flora leading to toxicityResistance in fungi lacking functional cytosine deaminase
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Interacting drugs

5-Fluorocytosine
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Biomarkers

Expression of cytosine deaminase (for predicting efficacy of 5-fluorocytosine- or 5-fluorouracil-based therapies)

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