Synthetically lethal interactions involving loss of the yeast ERG24: the sterol C-14 reductase gene.

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.

Cumulative mutations affecting sterol biosynthesis in the yeast Saccharomyces cerevisiae result in synthetic lethality that is suppressed by alterations in sphingolipid profiles.

UPC2 and ECM22 belong to a Zn(2)-Cys(6) family of fungal transcription factors and have been implicated in the regulation of sterol synthesis in Saccharomyces cerevisiae and Candida albicans. Previous reports suggest that double deletion of these genes in S. cerevisiae is lethal depending on the genetic background of the strain. In this investigation we demonstrate that lethality of upc2Delta ecm22Delta in the S288c genetic background is attributable to a mutation in the HAP1 transcription factor. In addition we demonstrate that strains containing upc2Delta ecm22Delta are also inviable when carrying deletions of ERG6 and ERG28 but not when carrying deletions of ERG3, ERG4, or ERG5. It has previously been demonstrated that UPC2 and ECM22 regulate S. cerevisiae ERG2 and ERG3 and that the erg2Delta upc2Delta ecm22Delta triple mutant is also synthetically lethal. We used transposon mutagenesis to isolate viable suppressors of hap1Delta, erg2Delta, erg6Delta, and erg28Delta in the upc2Delta ecm22Delta genetic background. Mutations in two genes (YND1 and GDA1) encoding apyrases were found to suppress the synthetic lethality of three of these triple mutants but not erg2Delta upc2Delta ecm22Delta. We show that deletion of YND1, like deletion of GDA1, alters the sphingolipid profiles, suggesting that changes in sphingolipids compensate for lethality produced by changes in sterol composition and abundance.

Antimicrobial activity and cytotoxicity of Aerva lanata.

Aerva lanata whole plant showed interesting antimicrobial activities (ethyl acetate and methanol extracts) and significant cytotoxic properties (petroleum ether, ethyl acetate and methanol extracts).