Dynamics of the compartmentalized Streptomyces chromosome during metabolic differentiation

Virginia S Lioy,Nelle Varoquaux,Corinne Saulnier,Sylvie Lautru,Soumaya Najah,Thibault Poinsignon,Kevin Gorrichon,Pierre Leblond,Bertrand Aigle,Jean-Noël Lorenzi,Yan Jaszczyszyn,Frédéric Boccard,Hervé Leh,Stéphanie Bury-Moné,Annabelle Thibessard,Jean-Luc Pernodet,Olivier Lespinet,Ivan Junier

doi:10.1038/s41467-021-25462-1

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.

Highlights

Bacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics
We mapped the genes encoding the ‘actinobacterial signature’ previously identified[34] as those coding sequences (CDSs) that are nearly universal among actinobacteria
Genes from the core, the actinobacterial signature, and/or presenting a high level of persistence are enriched in the central region, whereas GIs and unique CDSs are enriched in chromosome extremities

Summary

Introduction

Bacteria of the genus Streptomyces are prolific producers of specialized metabolites, including antibiotics. 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. The terminal arms are mainly composed of conditionally adaptive genes, in particular, enriched in specialized metabolite biosynthetic gene clusters (SMBGCs)[14] They are prone to large DNA rearrangements and frequent recombination[12,15,16,17,18,19]. We explore the dynamics of Streptomyces ambofaciens ATCC 23877 linear chromosome during metabolic differentiation This strain, well-studied for its genome organization and plasticity[12,16,17,30], is industrially exploited for the production of spiramycin. Our results highlight a link between chromosome folding, gene expression and genome evolution

Methods

Results

Conclusion