Thesis (Ph.D.) - Cairo University - Faculty of Pharmacy - Department of Microbiology and Immunology

The gut microbiota enriches the human gene pool and contributes to xenobiotic metabolism. For example, microbial azoreductases modulate the reduction of azo-bonds, activating produgs and azo polymer-coated dosage forms, or degrading food additives. Here we aimed atinvestigating different aspects of azoreductases in the human gut microbiome by constructing a specialized refined database for azodye-degrading enzymes to explore their evolutionary relationships, functional sites and structural properties; and by mining public gut and skin metagenomic for novel enzyme variants sets using various bioinformatics tools. Our database represents a core set of which to add any new sequences coding for azodyes degrading enzymes showed the dominance of phyla gamma-Proteobacteria and Firmicutes as well as NADH-dependency. A color-coded similarity matrix of the database delineated two main clusters of structural similarity belonging to different bacterial spices. Phylogenetic analysis of the database sequences distinguished three main clusters, two of which entirely made up of different Proteobacteria subphyla while the third gathered up all azoreductases of Firmicutes and Mycoplasma. Inner clustering of the database reduced its size to nearly 25%;yet the dominance of gamma-Proteobacteria and Firmicutes was not affected

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