Fungal fatty acid synthase (FAS)

Fungal fatty acid synthase (FAS) is a massive multienzyme complex responsible for the de novo synthesis of long-chain fatty acids, which are essential components of fungal cell membranes and signaling molecules. Unlike the individual enzymes found in bacteria (Type II FAS) or the single-polypeptide chain found in mammals, fungal FAS is a 2.6 MDa alpha6-beta6 heterododecameric complex that encapsulates all necessary catalytic activities within a protected reaction chamber (PMID: 17431170, 28439016). This structural divergence from human FAS makes it a highly attractive target for the development of narrow-spectrum antifungal agents. Inhibition of this complex leads to the depletion of essential lipids, resulting in loss of membrane integrity, growth arrest, and eventual cell death (PMID: 31603670). While several inhibitors like cerulenin have demonstrated potent antifungal activity in vitro, therapeutic application has been limited by toxicity and poor stability, driving ongoing research into more selective, non-covalent inhibitors (PMID: 25108033).

Other names

Fungal fatty acid synthase complexFatty acid synthetaseType I fungal fatty acid synthaseFAS1/FAS2 complex

Inhibition of the ketoacyl-synthase (KS) domain or other catalytic subunits within the multienzyme complex, preventing the condensation of acetyl-CoA and malonyl-CoA into long-chain fatty acids.