Physiological response of Saccharomyces cerevisiae to 15-azasterol-mediated growth inhibition.

We studied 15-aza-24-methylene-8,14-cholestadiene-3 beta-ol (15-azasterol) inhibition of Saccharomyces cerevisiae growth. Exposure to sublethal concentrations of this drug caused S. cerevisiae cells to undergo a transient period of inhibition at midlog phase. During growth inhibition the turbidity of each culture remained constant, as did the total cell number. Although the proportion of viable cells in cultures decreased from 90 to 12% during inhibition, methylene blue staining showed that less than 40% of the cells underwent metabolic inactivation. We monitored adenosine triphosphate levels throughout the inhibition cycle, and these levels followed kinetics identical to cell growth kinetics. After overcoming inhibition, cellular lipid extracts revealed the presence of a modified form of 15-azasterol. It appeared that the yeast cells were able to overcome 15-azasterol inhibition by an inactivating transmethylation reaction involving S-adenosylmethionine.