Pan-Genome of the Genus Streptomyces and Prioritization of Biosynthetic Gene Clusters With Potential to Produce Antibiotic Compounds

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.

Nigericin and Geldanamycin Are Phytotoxic Specialized Metabolites Produced by the Plant Pathogen Streptomyces sp. 11-1-2

“…hygroscopicus clade ( 32 , 33 ). Recently, an analysis of the Streptomyces pan-genome confirmed that 11-1-2 and S. hygroscopicus XM201 are closely related to each other and that both strains share more similarity at the genomic level with S. violaceusniger than with S. hygroscopicus , suggesting that they should be reclassified as S. violaceusniger ( 34 ). Plant-pathogenic Streptomyces strains are usually located within or near the S. scabiei clade.…”

Comparative genomic analysis of Streptomyces rapamycinicus NRRL 5491 and its mutant overproducing rapamycin

“…The SRMK07 strain showed the normal growth despite the large genomic deletions. This observation raised a question on the presence of core genes in this strain that are necessary for the normal growth; the core genes here refer to those present in genomes of the vast majority of biologically related organisms, for example, Streptomyces species in this study, likely because of the biological importance 29 , 30 . To examine the distribution of core genes in the SRMK07 strain’s genome, a software program ‘Antibiotic Resistant Target Seeker’ (ARTS) was used, which allows the detection of core genes, including housekeeping genes and resistance genes associated with BGCs 31 .…”

Ribosomal RNA operons define a central functional compartment in the Streptomyces chromosome

“…This allowed the identification of 1,017 ortholog genes associated with best reciprocal matches between coding sequences present in all 127 genomes, further defined as the 'core genome'. Interestingly, 943 of these genes (92.7 %) are included in the soft-core recently identified on a partially overlapping panel of Streptomyces genomes by Caicedo-Montoya et al (Roary method) (Caicedo-Montoya, Manzo-Ruiz, et Ríos-Estepa 2021). We used the position of the most external genes of the core genome as limits between the 'arms' and the 'core region' (that therefore includes all the core genes and some non-core genes, Fig.…”

“…We also identify two events of complete rrn operon loss by analyzing the phylogeny of Currie 2017; Lorenzi et al 2021;Caicedo-Montoya, Manzo-Ruiz, et Ríos-Estepa 2021). The number and completeness of rrn loci as well as rrn configuration and main intrachromosomal rearrangements are indicated for each strain as detailed in the legend panel.…”

“…previously described(McDonald et Currie 2017;Lorenzi et al 2021;Caicedo-Montoya, Manzo-Ruiz, et Ríos-Estepa 2021) division of the Streptomyces genus into two main monophyletic clades (clades '1' and '2') and other lineages further referred to as group 'O' (for 'others') (Figure2). By crossing this tree with genome nomenclature based on rrn categories and dnaA orientation, we propose a parsimonious scenario explaining the diversity observed in the panel of 127 analyzed genomes.…”