title: Plant sterol 14 alpha-demethylase affinity for azole fungicides.
abstract: Azole fungicides were thought to have much greater affinity for the fungal cytochrome P450 enzyme, sterol 14 alpha-demthylase (CYP51) than the plant orthologue. Using purified CYP51 from the plant Sorghum bicolor L Moenech, a direct comparison of the sensitivity to the fungicides triadimenol and tebuconazole has been carried out. S. bicolor CYP51 was purified to homogenity as determined by SDS--PAGE and specific heme content. Addition of the azole fungicides triadimenol and tebuconazole induced type II spectral changes, with saturation occurring at equimolar azole/P450 concentrations. Inhibition of reconstituted activities revealed only a threefold insensitivity of the plant CYP51 compared to a fungal CYP51, from the phytopathogen Ustilago maydis, as judged by IC(50) values. The implications for fungicide mode of action and application are discussed.
authors.affiliation: Institute of Biological Sciences, University of Wales, Aberystwyth SY23 3DA, United Kingdom.
authors.forename: D C
authors.initials: DC
authors.lastname: Lamb
authors.forename: M
authors.initials: M
authors.lastname: Cannieux
authors.forename: A G
authors.initials: AG
authors.lastname: Warrilow
authors.forename: S
authors.initials: S
authors.lastname: Bak
authors.forename: R A
authors.initials: RA
authors.lastname: Kahn
authors.forename: N J
authors.initials: NJ
authors.lastname: Manning
authors.forename: D E
authors.initials: DE
authors.lastname: Kelly
authors.forename: S L
authors.initials: SL
authors.lastname: Kelly
mesh_terms: D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics; D005656:Fungal Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D005659:Fungicides, Industrial / Q000378:metabolism / Q000494:pharmacology*; D020128:Inhibitory Concentration 50; D010088:Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010940:Plant Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013053:Spectrophotometry; D058886:Sterol 14-Demethylase; D014230:Triazoles / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D005656:Fungal Proteins; D005659:Fungicides, Industrial; D010940:Plant Proteins; D014230:Triazoles; C032910:triadimefon; C087114:tebuconazole; D003577:Cytochrome P-450 Enzyme System; D010088:Oxidoreductases; D058886:Sterol 14-Demethylase