Building synthetic chromosomes one yeast at a time: insights from Sc2.0

building-synthetic-chromosomes-one-yeast-at-a-time:-insights-from-sc2.0
Building synthetic chromosomes one yeast at a time: insights from Sc2.0
  • Comment
  • Published:

Nature Biotechnology (2025)Cite this article

Subjects

The Synthetic Yeast Genome Project (Sc2.0) set out to redesign and chemically synthesize an entire eukaryotic genome. This Comment summarizes the design- and construction-related defects revealed during the construction of 16 synthetic chromosomes, and the solutions applied, drawing out the key biological and technical insights that will inform future genome-scale engineering.

This is a preview of subscription content, access via your institution

Access options

Access Nature and 54 other Nature Portfolio journals

Get Nature+, our best-value online-access subscription

$32.99 / 30 days

cancel any time

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

  • Purchase on SpringerLink
  • Instant access to the full article PDF.

USD 39.95

Prices may be subject to local taxes which are calculated during checkout

References

  1. Richardson, S. M. et al. Science 355, 1040–1044 (2017).

    Article  CAS  PubMed  Google Scholar 

  2. Dymond, J. S. et al. Nature 477, 471–476 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Richardson, S. M., Nunley, P. W., Yarrington, R. M., Boeke, J. D. & Bader, J. S. Nucleic Acids Res. 38, 2603–2606 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Admire, A. et al. Genes Dev. 20, 159–173 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Ji, H. et al. Cell 73, 1007–1018 (1993).

    Article  CAS  PubMed  Google Scholar 

  6. Parenteau, J. et al. Mol. Biol. Cell 19, 1932–1941 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Parenteau, J. et al. Cell 147, 320–331 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Zhao, Y. et al. Cell 186, 5220–5236 (2023).

    Article  CAS  PubMed  Google Scholar 

  9. Xu, X. et al. Nat. Commun. 14, 1984 (2023).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Fredens, J. et al. Nature 569, 514–518 (2019).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Chen, L. G. et al. Nat. Plants 10, 228–239 (2024).

    Article  CAS  PubMed  Google Scholar 

  12. Goold, H. D., Moseley, J. L. & Lauersen, K. J. Cell Genomics 4, 100505 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Karas, B. J. et al. J. Biol. Eng. 7, 30 (2013).

    Article  PubMed  PubMed Central  Google Scholar 

  14. Gibson, D. G., Smith, H. O., Hutchison, C. A. III, Venter, J. C. & Merryman, C. Nat. Methods 7, 901–903 (2010).

    Article  CAS  PubMed  Google Scholar 

  15. Dai, J., Boeke, J. D., Luo, Z., Jiang, S. & Cai, Y. Genome Biol. 21, 205 (2020).

    Article  PubMed  PubMed Central  Google Scholar 

  16. Schindler, D. Bioeng. 7, 137 (2020).

    CAS  Google Scholar 

  17. Schindler, D., Walker, R. S. K. & Cai, Y. Cell Rep. Methods 4, 100761 (2024).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Robertson, W. E. et al. Nat. Protoc. 16, 2345–2380 (2024).

    Article  Google Scholar 

  19. Zürcher, J. F. et al. Nature 619, 555–562 (2023).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Ronda, C., Pedersen, L. E., Sommer, M. O. & Nielsen, A. T. Sci. Rep. 6, 19452 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Boeke, J. D. et al. Science 353, 126–127 (2016).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

Our Synthetic Yeast Genome Project (Sc2.0) work was supported by the Australian Research Council Centre of Excellence in Synthetic Biology and by external grants from Bioplatforms Australia, the New South Wales (NSW) Chief Scientist and Engineer, and the NSW Government’s Department of Primary Industries. Figures and tables were edited and refined by Bronte Turner of Serpentine Studio.

Author information

Authors and Affiliations

  1. School of Natural Sciences and ARC Centre of Excellence in Synthetic Biology, Macquarie University, Sydney, New South Wales, Australia

    Paige E. Erpf, Felix Meier, Roy S. K. Walker, Hugh D. Goold, Ian T. Paulsen & Isak S. Pretorius

  2. New South Wales Department of Primary Industries and Regional Development, Elizabeth Macarthur Agriculture Institute, Advanced Gene Technology Centre, Menangle, New South Wales, Australia

    Hugh D. Goold

  3. Institute for Systems Genetics, NYU Langone Health, New York, NY, USA

    Jef D. Boeke

  4. Department of Biochemistry and Molecular Pharmacology, NYU Langone Health, New York, NY, USA

    Jef D. Boeke

  5. Department of Biomedical Engineering, NYU Tandon School of Engineering, Brooklyn, NY, USA

    Jef D. Boeke

  6. The Australian Genome Foundry, Sydney, New South Wales, Australia

    Ian T. Paulsen

Authors

  1. Paige E. Erpf
  2. Felix Meier
  3. Roy S. K. Walker
  4. Hugh D. Goold
  5. Jef D. Boeke
  6. Ian T. Paulsen
  7. Isak S. Pretorius

Contributions

P.E.E., H.D.G., R.S.K.W., I.T.P. and I.S.P. conceived, developed and edited the manuscript, and K.M. and J.D.B. contributed to sections of the article and significantly helped with the refinement of the paper.

Corresponding authors

Correspondence to Ian T. Paulsen or Isak S. Pretorius.

Ethics declarations

Competing interests

The authors declare no competing interests.

Supplementary information

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Erpf, P.E., Meier, F., Walker, R.S.K. et al. Building synthetic chromosomes one yeast at a time: insights from Sc2.0. Nat Biotechnol (2025). https://doi.org/10.1038/s41587-025-02913-4

Download citation

  • Published:

  • Version of record:

  • DOI: https://doi.org/10.1038/s41587-025-02913-4