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The versatility of the fungal cytochrome P450 monooxygenase system is instrumental in xenobiotic detoxification
Author(s) -
Lah Ljerka,
Podobnik Barbara,
Novak Metka,
Korošec Branka,
Berne Sabina,
Vogelsang Matjaž,
Kraševec Nada,
Zupanec Neja,
Stojan Jure,
Bohlmann Joerg,
Komel Radovan
Publication year - 2011
Publication title -
molecular microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.857
H-Index - 247
eISSN - 1365-2958
pISSN - 0950-382X
DOI - 10.1111/j.1365-2958.2011.07772.x
Subject(s) - monooxygenase , xenobiotic , cytochrome p450 , detoxification (alternative medicine) , biology , biochemistry , secondary metabolism , enzyme , cyp2b6 , cytochrome , metabolism , drug metabolism , biosynthesis , cyp1a2 , medicine , alternative medicine , pathology
Summary Cytochromes P450 (CYPs) catalyse diverse reactions and are key enzymes in fungal primary and secondary metabolism, and xenobiotic detoxification. CYP enzymatic properties and substrate specificity determine the reaction outcome. However, CYP‐mediated reactions may also be influenced by their redox partners. Filamentous fungi with numerous CYPs often possess multiple microsomal redox partners, cytochrome P450 reductases (CPRs). In the plant pathogenic ascomycete Cochliobolus lunatus we recently identified two CPR paralogues, CPR1 and CPR2. Our objective was to functionally characterize two endogenous fungal cytochrome P450 systems and elucidate the putative physiological roles of CPR1 and CPR2. We reconstituted both CPRs with CYP53A15, or benzoate 4‐hydroxylase from C. lunatus , which is crucial in the detoxification of phenolic plant defence compounds. Biochemical characterization using RP‐HPLC shows that both redox partners support CYP activity, but with different product specificities. When reconstituted with CPR1, CYP53A15 converts benzoic acid to 4‐hydroxybenzoic acid, and 3‐methoxybenzoic acid to 3‐hydroxybenzoic acid. However, when the redox partner is CPR2, both substrates are converted to 3,4‐dihydroxybenzoic acid. Deletion mutants and gene expression in mycelia grown on media with inhibitors indicate that CPR1 is important in primary metabolism, whereas CPR2 plays a role in xenobiotic detoxification.