Abstract
Species of the genus Streptomyces are known for their ability to produce multiple secondary metabolites; their genomes have been extensively explored to discover new bioactive compounds. The richness of genomic data currently available allows filtering for high quality genomes, which in turn permits reliable comparative genomics studies and an improved prediction of biosynthetic gene clusters (BGCs) through genome mining approaches. In this work, we used 121 genome sequences of the genus Streptomyces in a comparative genomics study with the aim of estimating the genomic diversity by protein domains content, sequence similarity of proteins and conservation of Intergenic Regions (IGRs). We also searched for BGCs but prioritizing those with potential antibiotic activity. Our analysis revealed that the pan-genome of the genus Streptomyces is clearly open, with a high quantity of unique gene families across the different species and that the IGRs are rarely conserved. We also described the phylogenetic relationships of the analyzed genomes using multiple markers, obtaining a trustworthy tree whose relationships were further validated by Average Nucleotide Identity (ANI) calculations. Finally, 33 biosynthetic gene clusters were detected to have potential antibiotic activity and a predicted mode of action, which might serve up as a guide to formulation of related experimental studies.
Highlights
Streptomyces is the most prolific genus of the phylum Actinobacteria in terms of secondary metabolites production with high societal impact
We present the first comparative genomic study for the genus Streptomyces with a large amount of complete and high-quality genomes available, unveiling the pan-genome in terms of protein sequence similarity and protein domains content, describing phylogenetic relationships of the analyzed genomes, as well as highlighting the variability of their intergenic regions (IGRs) and their capability of producing bioactive compounds; the study prioritizes in the biosynthetic gene clusters (BGCs) with potential antibiotic activity and a predicted mode of action according to the co-localization of duplicated self-resistance genes
High quality genomes were included in the present investigation; apart from the status as “Complete genomes,” all genomes showed a high completeness and a reduced number of fragmented and missing genes (Supplementary Figure S1)
Summary
Streptomyces is the most prolific genus of the phylum Actinobacteria in terms of secondary metabolites production with high societal impact. It is estimated that members of the genus Streptomyces produce more than 50% of bioactive compounds produced by bacteria (Doroghazi and Metcalf, 2013). The advent of next-generation sequencing technologies unveiled the metabolic potential of bacteria as producers of secondary metabolites. Streptomyces coelicolor, for instance, only produces actinorhodin, undecylprodigiosin, calcium-dependent antibiotic and methylenomycin at laboratory conditions, though its genome contains over 20 biosynthetic gene clusters (Challis and Hopwood, 2003). The rapid progress on genomic sequencing and the decrease in sequencing prices have enabled obtaining a vast quantity of genomes that has led to a deeper knowledge of microorganisms capable of synthesizing bioactive compounds, and the discovery of biosynthetic gene clusters that might produce novel compounds with clinical and commercial value (Kalkreuter et al, 2020)
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