Abstract
Among various isoprenoid compounds, 1-geranylgeranylpyridinium (GGPy) showed remarkable lethal effects on Saccharomyces cerevisiae cells similarly under hypo- and hyperosmotic conditions at 30ºC. In addition to such osmotic stress, GGPy exhibited temperature-dependent lethal effects against S. cerevisiae and the pathogenic yeast Candida albicans at the human body temperature of 37ºC. Fatty acid synthase (FAS) was identified as one of the GGPy-binding proteins and was considered a molecular target of GGPy in its inhibitory effect on the fungal stress adaptation. GGPy was not inhibitory to the activity of FAS assayed upon NADPH oxidation involved in acyl chain elongation by this multi-functional enzyme complex. Nevertheless, the lethality of GGPy was repressed in the medium where polyoxyethylene sorbitan monopalmitate (Tween 40) supplemented as the water-soluble and esterase dependent source of palmitic acid. These findings may suggest that GGPy is permissive for acetyl unit incorporation into the growing chain of fatty acyl-CoA by FAS butis restrictive to its ultimate elongation to palmitoyl-CoA as a donor of the long-chain saturated fatty acid for the synthesis of stress-tolerant glycerophospholipids.
Highlights
Among various isoprenoid compounds, 1- resulting activation of β-1, 3-glucan synthase (Inoue et geranylgeranylpyridinium (GGPy) showed remarkable lethal al., 1999; Levin, 2005)
We found the by targeting β-1, 3-glucan synthase
We first examined the lethal effects of GGPy in distilled water (DW), YPD medium, and YPD medium with D-sorbitol added as an osmotic stabilizer to estimate its relation to the loss of cell wall integrity
Summary
1- resulting activation of β-1, 3-glucan synthase (Inoue et geranylgeranylpyridinium (GGPy) showed remarkable lethal al., 1999; Levin, 2005). E) Assays of enzyme activities The activity of GAPDH was determined using the reaction mixture containing 1.0 mM NAD+, 10 mM EDTA, 0.1 mM dithiothreitol, 4.0 mM glyceraldehyde-3phosphate, and the enzyme in 100 mM potassium a) Effects of GGPy on the cell viability of S. cerevisiae under various osmotic conditions
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