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

Dariusz R. Kutyna; Cristobal A. Onetto; Thomas C. Williams; Hugh D. Goold; Ian T. Paulsen; Isak S. Pretorius; Daniel L. Johnson; Anthony R. Borneman

doi:10.1038/s41467-022-31305-4

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

Dariusz R. Kutyna, Cristobal A. Onetto, Thomas C. Williams, Hugh D. Goold, Ian T. Paulsen, Isak S. Pretorius, Daniel L. Johnson, Anthony R. Borneman^*

^*Corresponding author for this work

Deputy Vice-Chancellor (Research) - Office

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Abstract

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.

Original language	English
Article number	3628
Pages (from-to)	1-9
Number of pages	9
Journal	Nature Communications
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41467-022-31305-4
Publication status	Published - 24 Jun 2022

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Copyright the Author(s) 2022. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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abstract = "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.",

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AU - Paulsen, Ian T.

AU - Pretorius, Isak S.

AU - Johnson, Daniel L.

AU - Borneman, Anthony R.

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

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