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Designing minimal genomes using whole-cell models

Author

Listed:
  • Joshua Rees-Garbutt

    (University of Bristol
    University of Bristol)

  • Oliver Chalkley

    (University of Bristol
    University of Bristol
    University of Bristol)

  • Sophie Landon

    (University of Bristol
    University of Bristol)

  • Oliver Purcell

    (Engine Biosciences, MBC Biolabs)

  • Lucia Marucci

    (University of Bristol
    University of Bristol
    University of Bristol)

  • Claire Grierson

    (University of Bristol
    University of Bristol)

Abstract

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.

Suggested Citation

  • Joshua Rees-Garbutt & Oliver Chalkley & Sophie Landon & Oliver Purcell & Lucia Marucci & Claire Grierson, 2020. "Designing minimal genomes using whole-cell models," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-14545-0
    DOI: 10.1038/s41467-020-14545-0
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    Cited by:

    1. Simeon D. Castle & Michiel Stock & Thomas E. Gorochowski, 2024. "Engineering is evolution: a perspective on design processes to engineer biology," Nature Communications, Nature, vol. 15(1), pages 1-10, December.

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