Designing Minimal Genomes Using Whole-Cell Models

Joshua Rees-Garbutt, Oliver Chalkley, Sophie Landon, Oliver Purcell, Lucia Marucci, Claire Grierson

Research output: Contribution to journalArticle (Academic Journal)peer-review

35 Citations (Scopus)
203 Downloads (Pure)


In the future, entire genomes tailored to specific functions and environments could be designed using computational tools. However, computational tools for genome design are currently scarce. Here we present algorithms that enable the use of design-simulate-test cycles for genome design, using genome minimisation as a proof-of-concept. Minimal genomes are ideal for this purpose as they have a simple functional assay whether the cell replicates or not. We used the first (and currently only published) whole-cell model for the bacterium Mycoplasma genitalium. Our computational design-simulate-test cycles discovered novel in-silico minimal genomes which, if biologically correct, predict in-vivo genomes smaller than JCVI-Syn3.0; a bacterium with, currently, the smallest genome that can be grown in pure culture. In the process, we identified 10 low essential genes and produced evidence for at least two Mycoplasma genitalium in-silico minimal genomes. This work brings combined computational and laboratory genome engineering a step closer.
Original languageEnglish
Article number836 (2020)
Number of pages12
JournalNature Communications
Publication statusPublished - 11 Feb 2020

Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute
  • Genome Design
  • Engineering Mathematics Research Group


  • Synthetic biology
  • genomic engineering
  • computer modelling


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