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Functional Genomics of Xenobiotic Detoxifying Fungal Cytochrome P450 System

Subramanian, Venkataramanan
http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204753142

Abstract Details

2008, PhD, University of Cincinnati, Medicine : Toxicology (Environmental Health).
The white rot fungus Phanerochaete chrysosporiumis primarily known for its ability to degrade a wide range of xenobiotic compounds including the highly recalcitrant polycyclic aromatic hydrocarbons. The natural substrate of this basidiomycete fungus is however, lignin, the most abundant aromatic polymer on earth. The versatililty of this fungus in breaking down a wide array of compounds arises from the presence of a highly nonspecific enzyme system (peroxidase enzyme system) in its repertoire. Most of the research involving degradation of toxic chemicals has focused on this biodegrading enzyme machinery. Cytochrome P450 monooxygenases (P450s) on the other hand, are heme-thiolate proteins that are known to be involved in metabolism of endogenous compounds as well as xenobiotic compounds in higher eukaryotes. Nearly 150 P450s are present in this organism, which is the highest number known till date among fungal species. Based on the sequence similarity criteria and our phylogenetic analysis, these P450s have been classified under 12 families and 23 sub-families. Despite indirect evidences suggesting the role of P450s in oxidation of xenobiotics, there have been hardly any reports on characterization and role of individual P450s either in regulation of physiological processes or in direct metabolism of xenobiotics in this organism. Here we characterized and investigated the role of P450 enzymes in two different mechanisms in this fungus. One, indirect involvement of P450s in peroxidase–mediated oxidation of xenobiotics, and two, direct involvement of P450s in metabolism of xenobiotics. In order to achieve the first objective, we investigated the role of PC-bphgene, the only member of the P450 CYP53 in synthesis of a secondary metabolite, veratryl alcohol, which regulates the activity of the peroxidase enzyme system of this fungus. In order to achieve the second objective, we used the functional genomic approach based on a custom-designed microarray and heterologous expression of the components of the P450 enzyme system (P450 and its associated electron transfer proteins) in this white rot fungus.
Dr. Jagjit Yadav (Advisor)
232 p.
Phanerochaete chrysosporium; Cytochrome P450; White rot fungus; lignin degradation; xenobiotic degradation; Microarray; RT-PCR; Heterologous expression; HPLC analysis; Piperonyl butoxide; siRNA; RNA interference; Peroxidases; P450 oxidoreductase

Recommended Citations

Citations

  • Subramanian, V. (2008). Functional Genomics of Xenobiotic Detoxifying Fungal Cytochrome P450 System [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204753142

    APA Style (7th edition)

  • Subramanian, Venkataramanan. Functional Genomics of Xenobiotic Detoxifying Fungal Cytochrome P450 System. 2008. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204753142.

    MLA Style (8th edition)

  • Subramanian, Venkataramanan. "Functional Genomics of Xenobiotic Detoxifying Fungal Cytochrome P450 System." Doctoral dissertation, University of Cincinnati, 2008. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1204753142

    Chicago Manual of Style (17th edition)

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© 2008, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.