Comparative Anlysis of Cytochrome P450 monooxygenase in pathogenic eurotiomycetes
2133600-57150 THE VIABILITY OF IN-SILICO ANALYSIS OF CYP51s IN EUROTIOMYCETES SPECIES FORIDENTIFYING NOVEL AZOLE RESISTANCE MECHANISM By Students Name Thesis Submitted in fulfillment of the requirements of the degree Degree Department of Health Sciences Central University of Technology, Free State 01 December 2020 Supervisor Co-supervisor DECLARATION ABSTRACT The classification and characterization of cytochrome P450 monooxygenases in Eurotiomycetes species of fungus have unfolded various structure-function correlates of the enzyme and its variants from the perspective of evolutionary history and drug resistance. The present thesis explored the attributes of azole resistance of Aspergillus strains in terms of point mutations and polymorphisms in CYP51 and CYP51. The azole resistance in Eurotiomycetes was studied Aspergillus fumigatus as the case study. Studies reveal that Aspergillus houses CYP51A and CYP51B and both of them are required for functionality of the CYP51. The CYP51 is chemically 14-alpha demethylase that converts lanosterol to ergosterol. Ergosterol helps in the membrane fluidity and virulence of the fungal isolate. The enzyme is a putative target of azoles, especially the active heme molecule within the active site. The present study was based on in-silico analysis that involved BLAST, FASTA, phylogenetic analysis, and protein modeling to explore the novel single nucleotide polymorphisms and point mutations and its extrapolation to CYP51 structures as enlisted in the…
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