Ergosterol Synthesis Pathway

The ergosterol synthesis pathway is a complex, multi-step metabolic process found primarily in fungi and some protozoa. It is responsible for the production of ergosterol, a sterol that serves as a critical component of fungal cell membranes, analogous to cholesterol in animal cells. The pathway involves numerous enzymes and regulatory mechanisms and is essential for fungal viability, making it an important target for antifungal drug development. It consists of three main modules: the Mevalonate pathway, Farnesyl Pyrophosphate biosynthesis, and Ergosterol biosynthesis. Key enzymes include ERG10, HMG1/HMG2, ERG9, ERG1, ERG7, and ERG11 (CYP51). Regulation occurs at transcriptional, translational, and posttranslational levels. Most late-stage reactions occur on the endoplasmic reticulum membrane, and ergosterols are transported to the plasma membrane or stored as steryl esters within lipid droplets. Enzymes unique or essential within this pathway are prime targets for antifungal drugs, such as azoles targeting ERG11. Disruption leads to loss of cell membrane integrity/functionality and ultimately fungal death.

Inhibition of ergosterol biosynthesis enzymes, leading to disruption of fungal cell membrane integrity and function.