Sterol Biosynthesis Inhibitors and Anti-Feeding Compounds

Living organisms are separated from the outside world by their membranes, which perform important roles for maintaining their lives. Sterols are indispensable com- ponents in eukaryotic organisms for stabilizing membranes composed of phospho- lipid bilayers. Most prokaryotic organisms, on the other hand, do not contain sterols in their membranes, although recent studies indicated that the bacterium Methylo- coccus capsulatus produces sterols 1) and many strains of Mycoplasma, bacteria without cell walls, require sterols as an essential growth factor 2). Some bacterial species synthesize hopanoids which are hypothesized to function like st~rols in eu- karyotic organisms 3). Significance of ergosterol in fungi has been recognized from the fact that the yeast Saccharomyces cerevisiae requires ergosterol for growth, when cultured in a strictly anaerobic condition "'. l:.lectron microscopic studies showed that membrane structures disappeared in the yeast grown anaerobically without a supplement of ergosterol 5.6), indicating the necessity of ergosterol for membrane biogenesis.
Further confirmation of the significant role of ergosterol in the membranes was derived from the studies on polyene antibiotics. In the presence of polyenes such as nystatin, filipin and amphotericin B, fungal cells lose selective permeability of the membranes, since polyenes interact with ergosterol, such that the structure of the fungal membranes is disrupted 7).