4.8 Article

Construction of a synthetic Saccharomyces cerevisiae pan-genome neo-chromosome

Journal

NATURE COMMUNICATIONS
Volume 13, Issue 1, Pages -

Publisher

NATURE PORTFOLIO
DOI: 10.1038/s41467-022-31305-4

Keywords

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Funding

  1. Australian Government
  2. Bioplatforms Australia
  3. New South Wales (NSW) Chief Scientist and Engineer
  4. NSW Government's Department of Primary Industries
  5. Australian Research Council

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The Synthetic Yeast Genome Project (Sc2.0) aims to design and build the next generation of industrial microbes. To address the lack of phenotypic diversity in the laboratory strain, researchers created a new chromosome containing diverse pan-genomic elements. This provides phenotypic plasticity to the Sc2.0 parent strain and expands its range of applicable carbon sources.
The Synthetic Yeast Genome Project (Sc2.0) represents the first foray into eukaryotic genome engineering and a framework for designing and building the next generation of industrial microbes. However, the laboratory strain S288c used lacks many of the genes that provide phenotypic diversity to industrial and environmental isolates. To address this shortcoming, we have designed and constructed a neo-chromosome that contains many of these diverse pan-genomic elements and which is compatible with the Sc2.0 design and test framework. The presence of this neo-chromosome provides phenotypic plasticity to the Sc2.0 parent strain, including expanding the range of utilizable carbon sources. We also demonstrate that the induction of programmable structural variation (SCRaMbLE) provides genetic diversity on which further adaptive gains could be selected. The presence of this neo-chromosome within the Sc2.0 backbone may therefore provide the means to adapt synthetic strains to a wider variety of environments, a process which will be vital to transitioning Sc2.0 from the laboratory into industrial applications. The Sc2.0 consortia is reengineering the yeast genome. To expand the Sc2.0 genetic repertoire, the authors build a neo-chromosome comprising variable loci from diverse yeast isolates, providing phenotypic plasticity for use in synthetic backgrounds.

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