Cloning of the late genes in the ergosterol biosynthetic pathway ofSaccharomyces cerevisiae—A review

  title={Cloning of the late genes in the ergosterol biosynthetic pathway ofSaccharomyces cerevisiae—A review},
  author={Norman D. Lees and B A Skaggs and Donald R. Kirsch and Martin Bard},
Research on the ergosterol biosynthetic pathway in fungi has focused on the identification of the specific sterol structure required for normal membrane structure and function and for completion of the cell cycle. The pathway and its end product are also the targets for a number of antifungal drugs. Identification of essential steps in ergo-sterol biosynthesis could provide new targets for the development of novel therapeutic agents. Nine of the eleven genes in the portion of the pathway… 
Involvement of FgERG4 in ergosterol biosynthesis, vegetative differentiation and virulence in Fusarium graminearum.
The results of this study indicate that FgERG4 plays a crucial role in ergosterol biosynthesis, vegetative differentiation and virulence in the filamentous fungus F. graminearum.
Studies on Biosynthetic Genes and Enzymes of Isoprenoids Produced by Actinomycetes
  • T. Dairi
  • Biology
    The Journal of Antibiotics
  • 2005
Diterpene cyclases possessing unique primary structures that differ from those of eukaryotes and catalyze unique reactions are identified, which suggested that all the actinomycete strains possessing both the MV and MEP pathways produce isoprenoid compounds.
The results support the Bloch hypothesis, which postulates that the properties of sterols are gradually optimized for function along the biosynthetic pathway and provide a response to the enduring question “why ergosterol in fungi?”.
Ergosterol biosynthesis pathway in Aspergillus fumigatus
Elimination of the last reactions in ergosterol biosynthesis alters the resistance of Saccharomyces cerevisiae to multiple stresses
The constructed single or double gene deletion mutants of the last four enzymes in ergosterol biosynthesis in a prototrophic genetic background of Saccharomyces cerevisiae showed altered resistances to different exogenous stresses regarding the specific growth rate and duration of lag phase and suggest the possibility of improving the robustness of industrial yeast strains by engineering their sterol composition.
Analysis of the ergosterol biosynthesis pathway cloning, molecular characterization and phylogeny of lanosterol 14 α-demethylase (ERG11) gene of Moniliophthora perniciosa
Comparison of the protein sequences and phylogenetic analysis revealed that the M. perniciosa enzyme was most closely related to that of Coprinopsis cinerea, the causal agent of witches' broom disease of cocoa.
ERG6 gene deletion modifies Kluyveromyces lactis susceptibility to various growth inhibitors
The ERG6 gene encodes an S‐adenosylmethionine dependent sterol C‐24 methyltransferase in the ergosterol biosynthetic pathway. In this work we report the results of functional analysis of the
Preservation of Genes Involved in Sterol Metabolism in Cholesterol Auxotrophs: Facts and Hypotheses
A more parsimonious way is proposed to explain their accelerated evolution and subsequent stabilization in the case of the nematode and the fruitfly, which would have lost their ancestral function in cholesterogenesis but would have retained the other function(s), which keep them under pressure.


Sterol synthesis and viability oferg11 (cytochrome P450 lanosterol demethylase) mutations inSaccharomyces cerevisiae andCandida albicans
Results show that these double disruption strains are viable and that spontaneously arising suppressors of theERG11 disruption areerg3 mutants, compared to similar mutants ofCandida albicans that are viable in the absence of theerg3 lesion.
Cloning and disruption of the yeast C-8 sterol isomerase gene
Results suggest that the C-8 sterol isomerase activity is not essential for yeast cell viability, and represents the second ergosterol biosynthetic gene in the distal portion of the pathway to be disrupted without adversely affecting cell viability.
The yeast gene ERG6 is required for normal membrane function but is not essential for biosynthesis of the cell-cycle-sparking sterol
Although erg6 delta cells are unable to methylate ergosterol precursors at C-24, they exhibit normal vegatative growth, suggesting that C-28 sterols are not essential in S. cerevisiae, however, erg 6 delta cells exhibit pleiotropic phenotypes that include defective conjugation, hypersensitivity to cycloheximide, resistance to nystatin, severely diminished capacity for genetic transformation, and defective tryptophan uptake.
Molecular cloning, characterization, and overexpression of ERG7, the Saccharomyces cerevisiae gene encoding lanosterol synthase.
Two overlapping clones were assembled to make a functional reconstruction of the ERG7 gene, which contains a 2196-bp open reading frame capable of encoding an 83-kDa protein, and the reconstruction complemented the erg7 mutation when driven from either its native promoter or the strong ADH1 promoter.
Molecular cloning and characterization of the yeast gene for squalene synthetase.
Disruption of the chromosomal squalene synthetase coding region by insertional mutagenesis indicates that ERG9 is a single copy gene that is essential for cell growth in yeast.
Cloning, sequencing, and disruption of the gene encoding sterol C-14 reductase in Saccharomyces cerevisiae.
A sterol C-14 reductase (erg24-1) mutant of Saccharomyces cerevisiae was selected in a fen1, fen2, suppressor background on the basis of nystatin resistance and ignosterol (ergosta-8,14-dienol)
Requirement for a second sterol biosynthetic mutation for viability of a sterol C-14 demethylation defect in Saccharomyces cerevisiae
Growth studies with a sterol auxotrophic strain indicated that the major sterol of strain JR4, 14 alpha-methyl-ergosta-8,24(28)-dien-3 beta-ol, could satisfy "bulk" membrane requirements but not the second, structurally specific, sterol function that was defined previously.
Structural discrimination in the sparking function of sterols in the yeast Saccharomyces cerevisiae
The native sterol, ergosterol, initiated growth faster and allowed a greater cell yield than did other sterols selectively altered in one or more features of the sterol.