Genetical and Biochemical Aspects of Resistance to p-Fluorophenylalanine in Saccharomyces cerevisiae

SUMMARY: Growth of haploid yeast strains was inhibited by the phenylalanine (PA) analogue dl-p-fluorophenylalanine (FPA) in yeast extract media containing 0·2 mg PA/ml. Most strains had a maximum FPA tolerance of about 0·25 mg/ml when glycerol was the carbon source and 0·5 mg/ml in glucose medium. Spontaneous FPA-resistant mutants isolated on glucose medium showed little or no increase in FPA tolerance over that of the parent when metabolizing glycerol. Resistance was controlled by a different nuclear gene in each of four mutants analysed. In a proportion of the mutants the amount of FPA incorporated into cellular proteins in competition with PA was less than into the proteins of sensitive parental cells, whether glucose or glycerol was used as carbon source. This suggests that the mutational change allowed the cytoplasmic system to discriminate against the analogue without affecting its incorporation into mitochondrially-synthesized proteins. Although attempts to measure the latter were not made, the observed decrease in respiratory activity of cells grown in the presence of FPA suggests such incorporation. In other mutants showing resistance to FPA in glucose medium, the amount of FPA incorporated into cellular proteins varied with the carbon source, less analogue being incorporated in glucose medium than in glycerol medium.