Dynamics of the compartmentalizedStreptomyceschromosome during metabolic differentiation

Abstract

Streptomyces are among the most prolific bacterial producers of specialized metabolites, including antibiotics. The linear chromosome is partitioned into a central region harboring core genes and two extremities enriched in specialized metabolite biosynthetic gene clusters (SMBGCs). The molecular mechanisms governing structure and function of these compartmentalized genomes remain mostly unknown. Here we show that in exponential phase, chromosome structure correlates with genetic compartmentalization: conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends are transcriptionally, largely quiescent compartments with different structural features. Onset of metabolic differentiation is accompanied by remodeling of chromosome architecture from an ‘open’ to a rather ‘closed’ conformation, in which the SMBGCs are expressed forming new boundaries. Altogether, our results reveal that S. ambofaciens’ linear chromosome is partitioned into structurally distinct entities, indicating a link between chromosome folding, gene expression and genome evolution.

Bilateral symmetry of linear streptomycete chromosomes

“…4a). Synteny is reduced towards the telomeres in comparison with the core region of the chromosome and likely reflects the genetic compartmentalization of streptomycete chromosomes that is consistent with the demonstration of a link between chromosome folding and gene expression in Streptomyces ambofaciens [54]. However, comparison of strains located at other phylogenetic nodes Fig.…”

“…Bacterial chromosomes display a high degree of organization with respect to the locations of core genes [54, 57]. In Bordetella pertussis , with a circular chromosome, there is a bias toward symmetrical inversions [58] for the maintenance of replichore balance and preservation of favourable gene arrangements.…”

“…It may be, therefore, that the conserved synteny of the origin island represents an irreducible axis around which recombination can take place, whilst not being subject to recombination itself. It also suggests that maintenance of an intact origin island is necessary for successful chromosome replication, segregation or appropriate compaction [ 54 ].…”

Evolution of genome fragility enables microbial division of labor

“…Based on the robustness of our results to parameter changes, and because genome instabilities are extremely common in Streptomyces , we expect that other species in the genus also divide labor through this mechanism. For instance, recent results show that expression of biosynthetic pathways in S. ambofaciens is related to DNA folding [44]. Based on our model, it is tempting to speculate that fragile siteinduced deletions can change DNA folding by removing parts of complementary DNA, exposing genes that were previously hidden to the transcription machinery.…”

Chromosomal organization of biosynthetic gene clusters, including those of nine novel species, suggests plasticity of myxobacterial specialized metabolism

“…Afforded complete or near-complete genome sequence data, we report the first comparative analysis of spatial organization of myxobacterial BGCs. Dissimilar from Streptomyces localization of BGCs in the extremities of linear genomes (Karoonuthaisiri et al, 2005;Lioy et al, 2021), clusters were distributed throughout the circular genomes of myxobacteria. Observed cluster-rich regions replete with modular BGCs, and noted inversions of biosynthetic genes could, however, contribute to metabolic differentiation similar to how terminal compartments of Streptomyces chromosomes enable spatial reorganization and conditional expression of BGCs during metabolic development and sporulation (Lioy et al, 2021).…”