Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

Abstract

Bacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. The linear chromosome includes a central region harboring core genes, as well as extremities enriched in specialized metabolite biosynthetic gene clusters. Here, we show that chromosome structure in Streptomyces ambofaciens correlates with genetic compartmentalization during exponential phase. Conserved, large and highly transcribed genes form boundaries that segment the central part of the chromosome into domains, whereas the terminal ends tend to be transcriptionally quiescent compartments with different structural features. The onset of metabolic differentiation is accompanied by a rearrangement of chromosome architecture, from a rather ‘open’ to a ‘closed’ conformation, in which highly expressed specialized metabolite biosynthetic genes form new boundaries. Thus, our results indicate that the linear chromosome of S. ambofaciens is partitioned into structurally distinct entities, suggesting a link between chromosome folding, gene expression and genome evolution.

Relationship between the Chromosome Structural Dynamics and Gene Expression—A Chicken and Egg Dilemma?

“…The genomic DNA within each CID seems to be organized into supercoiled plectonemic loops of at least 10-kb in size. Boundaries between the CIDs are frequently created by long and strongly transcribed genes, although not all highly transcribed genes are associated with boundaries [ 109 ]. In C. crescentus , it was shown that active transcription blocks supercoil diffusion but that not all supercoil diffusion barriers are CID boundaries [ 110 ].…”

“…Macrodomains were also identified in B. subtilis [ 112 ] but not in Caulobacter [ 117 ]. The macrodomains seem to be differentially regulated [ 5 ] and play functional roles in various DNA-related transactions such as replication and transcription [ 109 ]. Their properties seem to depend in part on active transcription, especially during the exponential growth phase [ 118 ].…”

MGCEP 1.0: A Genetic-Engineered Marine-Derived Chassis Cell for a Scaled Heterologous Expression Platform of Microbial Bioactive Metabolites

“…Previous studies have shown the dynamic gene expression and spatial chromosome arrangement from primary to secondary metabolism in Streptomyces. 55,56 However, studies of transcriptional changes in Streptomyces sp. as a chassis strain expressing heterologous BGCs are still rather rare.…”

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

“…We recently demonstrated that the genetic compartmentalization of Streptomyces ambofaciens ATCC 23877 correlates with chromosome architecture and gene expression in exponential phase ( 9 ). During vegetative growth, the distal ribosomal RNA ( rrn ) operons delimit a highly structured and expressed region termed ‘central compartment’, presenting structural features distinct from those of the terminal compartments which are almost transcriptionally quiescent ( 9 ). This led us to propose that these distal rrn operons may constitute some kind of barrier contributing to the evolution of Streptomyces genomes towards a compartmentalized organization ( 9 ).…”

“…During vegetative growth, the distal ribosomal RNA ( rrn ) operons delimit a highly structured and expressed region termed ‘central compartment’, presenting structural features distinct from those of the terminal compartments which are almost transcriptionally quiescent ( 9 ). This led us to propose that these distal rrn operons may constitute some kind of barrier contributing to the evolution of Streptomyces genomes towards a compartmentalized organization ( 9 ).…”