Communication Dans Un Congrès Année : 2022

Genome-scale engineering of Bacillus subtilis yields emergent phenotypes and allows to revisit concepts of minimal genomes

Etienne Dervyn
Anne-Gaëlle Planson
Kosei Tanaka
  • Fonction : Auteur
  • PersonId : 969464
Victor Chubukov
  • Fonction : Auteur
Cyprien Guérin
Sandra Dérozier
François Lecointe
Uwe Sauer
  • Fonction : Auteur
  • PersonId : 841574
Kenichi Yoshida
  • Fonction : Auteur
Pierre Nicolas
Philippe Noirot

Résumé

Genome-scale engineering enables rational removal of dispensable genes in chassis genomes. Deviating from this approach, we applied greedy accumulation of deletions of large dispensable regions in the Bacillus subtilis genome, yielding a library of 298 strains with genomes reduced up to 1.48 Mb in size. High‐throughput physiological phenotyping of these strains confirmed that genome reduction is associated with substantial loss of cell fitness and accumulation of synthetic-sick interactions. Transcriptome analysis indicated that most transcriptional changes can be explained by loss of known functions and by aberrant transcription at deletion boundaries. Genome-reduced strains also exhibited striking new phenotypes relative to wild type, including a very high resistance to DNA-damaging agents and a very low spontaneous mutagenesis. Adaptive laboratory evolution failed to restore cell fitness, except when coupled with a synthetic increase of the mutation rate, confirming low evolvability. Genome-scale engineering also enables rational construction of semi-synthetic genomes using in-vitro and in-yeast assembly methods. Following this strategy, we are building a library of semi-synthetic phages of B. subtilis, and a B. subtilis semi-synthetic genome to provide new insights on the concept of minimal genomes.

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Dates et versions

hal-05123414 , version 1 (20-06-2025)

Identifiants

  • HAL Id : hal-05123414 , version 1

Citer

Matthieu Jules, Etienne Dervyn, Anne-Gaëlle Planson, Kosei Tanaka, Victor Chubukov, et al.. Genome-scale engineering of Bacillus subtilis yields emergent phenotypes and allows to revisit concepts of minimal genomes. Bioengineering and Synthetic Biology, Nov 2022, Gif-sur-Yvette | Île-de-France, France. ⟨hal-05123414⟩
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