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Fungal nucleic acid synthesis involves the complex enzymatic machinery required for replicating fungal genomes and transcribing genetic information into functional RNA [1]. This biological process is a key therapeutic target for the antimetabolite class of antifungal drugs, most notably flucytosine (5-fluorocytosine) [2]. Within the fungal cell, flucytosine is converted by the fungal-specific enzyme cytosine deaminase into 5-fluorouracil, which subsequently inhibits thymidylate synthase to halt DNA synthesis and incorporates into RNA to disrupt protein translation [2][3]. Because human cells lack the cytosine deaminase enzyme, this pathway provides a basis for selective toxicity against pathogens [4]. Clinically, targeting this process is essential for treating severe systemic infections, such as cryptococcal meningitis and invasive candidiasis, often in combination with other antifungal classes [1][5].
Inhibition of thymidylate synthase (disrupting DNA synthesis) and incorporation of fluorinated ribonucleotides into RNA (disrupting protein synthesis) following intracellular conversion by cytosine deaminase [2][3].
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