Annotation and comparative analysis of P450s, their redox partners and secondary metabolite gene clusters in the bacterial phylum Bacteroidetes
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Date
2022-09
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Abstract
Species belonging to the bacterial phyla Bacteroidetes and Firmicutes represent over 90% of the gastrointestinal microbiota. Changes in the ratio of these two bacterial groups were found to have contrasting health effects, including obesity and inflammatory diseases. Despite the availability of many bacterial genomes, comparative genomic studies on the gene pools of these two bacterial groups concerning cytochrome P450 monooxygenases (P450s), ferredoxins, and secondary metabolite biosynthetic gene clusters (smBGCs) are not reported. Recently, an analysis of P450s, ferredoxins, and smBGCs in Firmicutesspecies has been reported. However, such studies on Bacteroidetes species have not been performed. This study is aimed to address this research gap. In this study, a thorough comparative analysis of P450s in the phylum Bacteroidetes has been carried out. P450 data mining and annotation of P450s in this phylum displayed 98 P450s in 77 species. It consisted of 130 genera, the Hymenobacter genus having the most P450s. Twenty-one P450 families were discovered, with CYP1103 dominating. Cluster analysis revealed 1298 smBGCs, with terpene being the most dominant. Out of the 98 P450s found in 334 Bacteroidetes species, only eight P450s (8.2 %) of seven Bacteroidetes species were found as part of the secondary metabolite BGCs. Genome data mining and annotation of ferredoxins in 104 Bacteroidetes species revealed the presence of 269 ferredoxins in their genomes. Among the Bacteroidetes species, Tenacibaculum jejuense had the highest number of ferredoxins (six). The 269 ferredoxins found in Bacteroidetes species can be grouped into five iron-sulfur (Fe-S) cluster types: 2Fe-2S, 3Fe-4S, 4Fe-4S, 2[4Fe-4S], and 2[4Fe-4S]Alv. The 7Fe-8S cluster-type ferredoxins were not found in the Bacteroidetesspecies analyzed in this study. Based on the amino acid spacing pattern analysis between the cysteine amino acids of the Fe-S cluster binding motif, 136 2Fe-2S ferredoxins of Bacteroidetes can be grouped into five subtypes. Eleven 4Fe-4S ferredoxins found in Bacteroidetes species can be grouped into three subtypes. The study revealed the presence of diverse sets of P450s, ferredoxins, and smBGCs in Bacteroidetes species genomes. Bacteroidetes species have the highest number of P450 families, ferredoxin cluster-types, and smBGCs compared to Firmicutes species. Only four P450 families, three ferredoxin cluster types, and five smBGCs are commonly shared between these two bacterial groups. Considering the above facts, we propose that the contrasting effects of these two bacterial groups on the host are partly due to the distinct nature of secondary metabolites produced by these organisms. Thus, the cause of the contrasting health effects of these two bacterial groups lies in their gene pools.
Description
A dissertation submitted in fulfilment of the requirement for the Degree of Master of Science in the Department of Biochemistry and Microbiology, Faculty of Science, Agriculture and Engineering, at the University of Zululand, 2022.