title: Role of P450 monooxygenases in the degradation of the endocrine-disrupting chemical nonylphenol by the white rot fungus Phanerochaete chrysosporium.
abstract: The white rot fungus Phanerochaete chrysosporium extensively degraded the endocrine disruptor chemical nonylphenol (NP; 100% of 100 ppm) in both nutrient-limited cultures and nutrient-sufficient cultures. The P450 enzyme inhibitor piperonyl butoxide caused significant inhibition (approximately 75%) of the degradation activity in nutrient-rich malt extract (ME) cultures but no inhibition in defined low-nitrogen (LN) cultures, indicating an essential role of P450 monooxygenase(s) in NP degradation under nutrient-rich conditions. A genome-wide analysis using our custom-designed P450 microarray revealed significant induction of multiple P450 monooxygenase genes by NP: 18 genes were induced (2- to 195-fold) under nutrient-rich conditions, 17 genes were induced (2- to 6-fold) in LN cultures, and 3 were induced under both nutrient-rich and LN conditions. The P450 genes Pff 311b (corresponding to protein identification number [ID] 5852) and Pff 4a (protein ID 5001) showed extraordinarily high levels of induction (195- and 167-fold, respectively) in ME cultures. The P450 oxidoreductase (POR), glutathione S-transferase (gst), and cellulose metabolism genes were also induced in ME cultures. In contrast, certain metabolic genes, such as five of the peroxidase genes, showed partial downregulation by NP. This study provides the first evidence for the involvement of P450 enzymes in NP degradation by a white rot fungus and the first genome-wide identification of specific P450 genes responsive to an environmentally significant toxicant.
authors: Environmental Genetics and Molecular Toxicology Division, Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, OH 45267-0056, USA.
authors: Venkataramanan
authors: V
authors: Subramanian
authors: Jagjit S
authors: JS
authors: Yadav
mesh_terms: D003470:Culture Media / Q000737:chemistry; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D015536:Down-Regulation; D052244:Endocrine Disruptors / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D015966:Gene Expression Regulation, Fungal; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020075:Phanerochaete / Q000378:metabolism*; D010636:Phenols / Q000378:metabolism*; D010882:Piperonyl Butoxide / Q000494:pharmacology; D015854:Up-Regulation
chemical_list: D003470:Culture Media; D065607:Cytochrome P-450 Enzyme Inhibitors; D052244:Endocrine Disruptors; D004791:Enzyme Inhibitors; D010636:Phenols; C025256:nonylphenol; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D010882:Piperonyl Butoxide