High impact information on Eburicol

• Eburicol and obtusifolione are unable to support cell growth, and the 3-ketosteroid has been shown to disturb membranes [1].
• The accumulation of obtusifolione as well as eburicol indicates that itraconazole inhibits not only the 14 alpha-demethylase but also (directly or indirectly) the NADPH-dependent 3-ketosteroid reductase, i.e., the enzyme catalyzing the last step in the demethylation at C-4 [1].
• Interestingly the binding site, beyond the C-3 position, contains a cleft which cannot accommodate a 4 beta-methyl substituent present in lanosterol or eburicol, the precursors of 14-desmethylsterols respectively in mammals and yeast [2].
• We used the nucleotide sequences of the gene that encodes eburicol 14alpha-demethylase (CYP51) and of the ribosomal DNA internal transcribed spacer 1 (ITS1), ITS2, and 5 [3].
• Resistance to sterol 14alpha-demethylase inhibiting fungicides (DMIs) has been correlated with mutations in the CYP51 gene, which encodes the target enzyme eburicol 14alpha-demethylase [4].

Biological context of Eburicol

• The CYP51 gene encoding eburicol 14 alpha-demethylase (P450(14DM)) was cloned from a genomic library of the filamentous fungal plant pathogen Penicillium italicum, by heterologous hybridisation with the corresponding gene encoding lanosterol 14 alpha-demethylase from the yeast Candida tropicalis [5].
• PCR cloning and detection of point mutations in the eburicol 14alpha-demethylase (CYP51) gene from Erysiphe graminis f. sp. hordei, a "recalcitrant" fungus [6].

Anatomical context of Eburicol

• No metabolism of lanosterol and eburicol, the substrates of the fungal and mammalian CYP51s, nor metabolism of herbicides and fatty acids was detected in the recombinant yeast microsomes [7].

Gene context of Eburicol

• In this paper we describe the effects of over-expression of the Penicillium italicum gene encoding eburicol 14 alpha-demethylase (cyp51), in Aspergillus niger strains with one or multiple copies of the gene encoding cytochrome P450 reductase (cprA), on the eburicol 14 alpha-demethylase activity [8].

Analytical, diagnostic and therapeutic context of Eburicol

• Cloning and sequence analysis of the eburicol 14alpha-demethylase gene of the obligate biotrophic grape powdery mildew fungus [9].
• A cloning strategy based on PCR has therefore been used to clone the eburicol 14alpha-demethylase (CYP51) gene of the obligate fungus Erysiphe graminis f. sp. hordei (Egh) using minute amounts of genomic DNA [6].

References