Target intelligence / Profile preview

Ergosterol biosynthesis pathway enzymes

Molecular classification
Enzyme, Cytochrome P450, Oxidoreductase, Isomerase, Methyltransferase, Lyase
01

Overview

The ergosterol biosynthesis pathway is a complex metabolic route in fungi responsible for the production of ergosterol, the primary sterol component of fungal cell membranes. Ergosterol performs essential structural and functional roles similar to cholesterol in animal cells, including the regulation of membrane fluidity, permeability, and the activity of membrane-bound proteins. The pathway involves a series of enzymatic reactions, starting from acetyl-CoA and proceeding through intermediates such as squalene and lanosterol. Key enzymes in this pathway, such as squalene epoxidase (ERG1) and lanosterol 14-alpha-demethylase (ERG11), are critical for fungal viability and serve as the primary targets for several classes of antifungal drugs. Inhibition of these enzymes leads to the depletion of ergosterol and the accumulation of toxic sterol precursors, which disrupts the fungal cell membrane and ultimately results in cell death. This pathway is a cornerstone of antifungal therapy, used to treat a wide range of infections from superficial skin conditions to invasive systemic mycoses.

Other names
Ergosterol biosynthetic pathwayFungal sterol biosynthesis pathwayErgosterol synthesis pathwayERG pathway
02

Mechanism of action

Inhibition of specific enzymes within the ergosterol biosynthesis pathway (e.g., Lanosterol 14-alpha-demethylase by azoles, Squalene epoxidase by allylamines, and C-14 reductase/C-8 isomerase by morpholines), leading to ergosterol depletion and the accumulation of toxic sterol intermediates that disrupt membrane integrity and function.

03

Biological functions

Sterol biosynthesisMembrane organization and biogenesisRegulation of membrane fluidityCell wall integritySignal transductionCell cycle regulationPheromone signaling
04

Disease associations

InfectionCandidiasisAspergillosisCryptococcosisDermatophytosisOnychomycosis
05

Safety considerations

HepatotoxicityDrug-drug interactions (via CYP450 inhibition)QT interval prolongationTeratogenicityEndocrine disruptionDevelopment of antifungal resistance
06

Interacting drugs

Fluconazole

13 more in the full profile.

07

Biomarkers

Ergosterol levelsLanosterol accumulationSqualene accumulation24(28) dehydroergosterol (24(28)DHE) levelsIgnosterol accumulationMinimum inhibitory concentration (MIC)

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