CYP51

Cytochrome P450 51 (CYP51), also known as sterol 14α-demethylase, catalyzes the removal of the 14α-methyl group from sterol precursors and constitutes an essential step in sterol biosynthesis across biological kingdoms^[1][2]. Mechanistically, CYP51 controls the production of membrane sterols, including cholesterol in vertebrates and ergosterol in fungi, thereby regulating membrane integrity, fluidity, and cellular viability^[3][4]. The enzyme occupies a central position in the ergosterol biosynthetic pathway, where inhibition of fungal CYP51 causes ergosterol depletion and accumulation of toxic sterol intermediates that suppress fungal growth^[5][6]. Consequently, CYP51 has become a major molecular target for clinical and agricultural azole antifungal agents, which bind the heme-containing active site and block sterol 14α-demethylation^[5][7]. In disease-related models, CYP51 inhibition is widely exploited for the treatment of invasive fungal infections and azole-resistant candidiasis, supporting its value in antifungal drug discovery and resistance studies^[8][9]. Compared with other cytochrome P450 isoforms, CYP51 is distinguished by its highly conserved catalytic function in sterol metabolism and broad evolutionary distribution across eukaryotes and some prokaryotes^[1][2]. Structural analyses further demonstrate that the conserved CYP51 ligand-binding cavity provides a robust framework for structure-guided development of selective inhibitors and mechanistic probes for sterol biosynthesis research^[3][10].