有哪些信誉好的足球投注网站a fungal p450 (cyp5136a3) capable of oxidizing polycyclic aromatic hydrocarbons and endocrine disrupting alkylphenols role of trp129 and leu324氧化能力的真菌p450(cyp5136a3)多环芳烃和内分泌扰乱trp129和leu324烷基的作用.pdfVIP
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a fungal p450 (cyp5136a3) capable of oxidizing polycyclic aromatic hydrocarbons and endocrine disrupting alkylphenols role of trp129 and leu324氧化能力的真菌p450(cyp5136a3)多环芳烃和内分泌扰乱trp129和leu324烷基的作用
A Fungal P450 (CYP5136A3) Capable of Oxidizing
Polycyclic Aromatic Hydrocarbons and Endocrine
Disrupting Alkylphenols: Role of Trp129 and Leu324
Khajamohiddin Syed, Aleksey Porollo, Ying Wai Lam, Jagjit S. Yadav*
Department of Environmental Health, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America
Abstract
The model white rot fungus Phanerochaete chrysosporium, which is known for its versatile pollutant-biodegradation ability,
possesses an extraordinarily large repertoire of P450 monooxygenases in its genome. However, the majority of these P450s
have hitherto unknown function. Our initial studies using a genome-wide gene induction strategy revealed multiple P450s
responsive to individual classes of xenobiotics. Here we report functional characterization of a cytochrome P450
monooxygenase, CYP5136A3 that showed common responsiveness and catalytic versatility towards endocrine-disrupting
alkylphenols (APs) and mutagenic/carcinogenic polycyclic aromatic hydrocarbons (PAHs). Using recombinant CYP5136A3,
we demonstrated its oxidation activity towards APs with varying alkyl side-chain length (C3-C9), in addition to PAHs (3–4
ring size). AP oxidation involves hydroxylation at the terminal carbon of the alkyl side-chain (v-oxidation). Structure-activity
analysis based on a 3D model indicated a potential role of Trp129 and Leu324 in the oxidation mechanism of CYP5136A3.
Replacing Trp129 with Leu (W129L) and Phe (W129F) significantly diminished oxidation of both PAHs and APs. The W129L
mutation caused greater reduction in phenanthrene oxidation (80%) as compared to W129F which caused greater
reduction in pyrene oxidation (88%). Almost complete loss of oxidation of C3-C8 APs (83–90%) was observed for the W129L
mutation as compared to W129F (28–41%). However, the tw
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