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Ergosterol biosynthesis pathway in fungi (None in standard use; occasionally "EBP" in literature, but not widely standardized)

Target
None in standard use; occasionally "EBP" in literature, but not widely standardized
Molecular classification
Enzyme pathway (metabolic pathway), Targeted enzymes include cytochrome P450 lanosterol 14α-demethylase (Erg11/Cyp51), squalene synthase (Erg9), C-5 sterol desaturase (Erg3), C-24 methyltransferase (Erg6), and others
01

Overview

The ergosterol biosynthesis pathway in fungi is a multi-enzyme metabolic pathway responsible for the production of ergosterol, the predominant sterol in fungal cell membranes. Ergosterol is essential for maintaining membrane structure, fluidity, and permeability, and is not found in human cells (which use cholesterol), making this pathway a selective antifungal target[1][2][3][5]. Major steps include the conversion of farnesyl diphosphate (FPP) to squalene, lanosterol, and ultimately ergosterol through a series of specific enzymes. Inhibition of key pathway enzymes disrupts fungal growth and survival, and forms the mechanistic basis for several major antifungal drug classes, notably azoles and polyenes[2][5]. Mutations in pathway enzymes are a common route to antifungal resistance, making the pathway central to both the development of new therapeutics and the monitoring of resistance[1][2][4][5]. Though ergosterol is the dominant sterol in most pathogenic fungi, some species produce alternative sterols through divergent pathways, which can have implications for drug sensitivity and resistance[4].

Other names
Ergosterol pathwaySterol biosynthesis (fungal-specific context)EBP (in some literature)
02

Mechanism of action

Inhibition of lanosterol 14α-demethylase (disrupts ergosterol synthesis, azoles); Inhibition of squalene epoxidase (blocks upstream sterol biosynthesis, allylamines); Direct binding and sequestration of ergosterol in membranes (polyenes); Blockage of other enzymatic steps (morpholines, etc.).

03

Biological functions

Membrane structure and integrityRegulation of membrane fluidity and permeabilityFungal survival, growth, and adaptation to stressQuorum sensing (via intermediates like farnesol)Virulence and pathogenicity
04

Disease associations

Infection (fungal diseases including candidiasis, aspergillosis, cryptococcosis)Antifungal resistance (role in drug adaptation and resistance emergence)
05

Safety considerations

Host toxicity from drugs (especially polyenes, e.g., nephrotoxicity with amphotericin B)Emergent antifungal resistanceDrug-drug interactions via broad specificity of some inhibitors (especially azoles impacting host sterol metabolism)
06

Interacting drugs

fluconazole

5 more in the full profile.

07

Biomarkers

Ergosterol levels in biological samples (indicator of fungal burden)Resistance mutations in pathway enzymes (e.g., Cyp51A, Cyp51B in Aspergillus)

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