STEROL SYNTHESIS AND VIABILITY OF ERG11 (CYTOCHROME-P450 LANOSTEROL DEMETHYLASE) MUTATIONS IN SACCHAROMYCES-CEREVISIAE AND CANDIDA-ALBICANS

The identification of the precise structural features of yeast sterol molecules required for the essential ''sparking'' function has been a controversial area of research. Recent cloning and gene disruption stu dies in Saccharomyces cerevisiae have shown that C-24 methylation (ERG 6), C-5 desaturation (ERG3) and Delta(8)-Delta(7) isomerization (ERG2) are not required, while C-14 demethylation (ERG11) and C-14 reduction (ERG24) are each required for aerobic viability. Earlier observations had indicated that C-14 demethylase deficient strains could be restor ed to aerobic growth by suppressor mutations that caused a deficiency in C-5 desaturase. These strains were reported to synthesize some ergo sterol, indicating that they contained leaky mutations in both ERG11 a nd ERG3, thereby making it impossible to determine whether the removal of the C-14 methyl group was required for aerobic viability. The avai lability of the ERG11 and ERG3 genes has been used in this study to co nstruct strains that contain null mutants in both ERG11 and ERG3. Resu lts show that these double disruption strains are viable and that spon taneously arising suppressors of the ERG11 disruption are erg3 mutants . The erg11 mutants of S. cerevisiae are compared to similar mutants o f Candida albicans that are viable in the absence of the erg3 lesion.