Biology Department, Indiana University-Purdue University Indianapolis, 723 West Michigan Street, Indianapolis, IN, 46202, USA, mbard@iupui-edu-
Abstract: ERG2 and ERG24 are yeast sterol biosynthetic genes which are targets of morpholine antifungal compounds- ERG2 and ERG24 encode the C-8 sterol isomerase and the C-14 reductase, respectively- ERG2 is regarded as a non-essential gene but the viability of ERG24 depends on genetic background, type of medium, and CaCl-2- concentration- We demonstrate that erg2 and erg24 mutants are viable in the deletion consortium background but are lethal when combined in the same haploid strain- The erg2erg24 double mutant can be suppressed by mutations in the sphingolipid gene ELO3 but not ELO2- Suppression occurs on rich medium but not on synthetic complete medium- We also demonstrate that the suppressed elo3erg2erg24 does not have a sterol composition markedly different from that of erg24- Further genetic analysis indicates that erg24 combined with mutations in erg6 or erg28 is synthetically lethal but when combined with mutations in erg3 is weakly viable- These results suggest that novel sterol intermediates probably contribute to the synthetic lethality observed in this investigation-