Cytochromes - Cytochomes P450 - ERG11 gene - Non-Elaborate Posts - Post 2

Erg11p performs a three-step oxidative C14-demethylation of lanosterol (and eburicol), yielding precursors that are further processed into ergosterol.  Erg11p performs a three-step oxidative C14-demethylation of lanosterol (and eburicol), yielding precursors that are further processed into ergosterol. Disrupting ERG11 is generally lethal: yeast lacking Erg11 activity cannot complete ergosterol synthesis and will not grow aerobically unless other suppressor mutations.

 Point mutations in ERG11 change one or a few amino acids in the Erg11 enzyme. Unlike a complete loss of ERG11 (which is usually lethal), many single substitutions allow the fungus to live, but these changes often impair normal sterol production. A complete ERG11 knockout cannot support aerobic growth. Even when the enzyme is nearly inactive, cells often require compensatodry mutations (for example in the downstream ERG3 gene) to survive. Many ERG11 point mutants accumulate 14α-methylated sterol intermediates. In one study, C. albicans and C. parapsilosis strains with the ERG11 Y132F mutation showed clear sterol changes, consistent with reduced Erg11 function. Mutant ERG11 strains may grow more slowly or be more sensitive to environmental stress due to weaker membranes. However, they remain viable because even the altered Erg11p can still make some ergosterol or because fungal cells tolerate alternative sterols.

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