Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Commentary
  • Published:

Upgrading protein synthesis for synthetic biology

Genetic code expansion for synthesis of proteins containing noncanonical amino acids is a rapidly growing field in synthetic biology. Creating optimal orthogonal translation systems will require re-engineering central components of the protein synthesis machinery on the basis of a solid mechanistic biochemical understanding of the synthetic process.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

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

Figure 1: Engineering efficient OTSs.
Figure 2: Chemical diversity of amino acids in the standard and expanded genetic codes.
Figure 3: Reassignment of CUN codons in yeast mitochondria provides insight into sense codon recoding.


  1. Crick, F.H.C. J. Mol. Biol. 38, 367–379 (1968).

    Article  CAS  Google Scholar 

  2. Ambrogelly, A., Palioura, S. & Söll, D. Nat. Chem. Biol. 3, 29–35 (2007).

    Article  CAS  Google Scholar 

  3. Campbell, J.H. et al. Proc. Natl. Acad. Sci. USA 110, 5540–5545 (2013).

    Article  CAS  Google Scholar 

  4. Böck, A. & Stadtman, T.C. Biofactors 1, 245–250 (1988).

    PubMed  Google Scholar 

  5. Gaston, M.A., Jiang, R. & Krzycki, J.A. Curr. Opin. Microbiol. 14, 342–349 (2011).

    Article  CAS  Google Scholar 

  6. Prat, L. et al. Proc. Natl. Acad. Sci. USA 109, 21070–21075 (2012).

    Article  CAS  Google Scholar 

  7. Bezerra, A.R. et al. Proc. Natl. Acad. Sci. USA 110, 11079–11084 (2013).

    Article  CAS  Google Scholar 

  8. Krishnakumar, R. et al. ChemBioChem (2013).

  9. Ruan, B. et al. Proc. Natl. Acad. Sci. USA 105, 16502–16507 (2008).

    Article  CAS  Google Scholar 

  10. Liu, C.C. & Schultz, P.G. Annu. Rev. Biochem. 79, 413–444 (2010).

    Article  CAS  Google Scholar 

  11. Park, H.S. et al. Science 333, 1151–1154 (2011).

    Article  CAS  Google Scholar 

  12. Wiltschi, B., Wenger, W., Nehring, S. & Budisa, N. Yeast 25, 775–786 (2008).

    Article  CAS  Google Scholar 

  13. O'Donoghue, P. et al. FEBS Lett. 586, 3931–3937 (2012).

    Article  CAS  Google Scholar 

  14. Mukai, T. et al. Nucleic Acids Res. 38, 8188–8195 (2010).

    Article  CAS  Google Scholar 

  15. Isaacs, F.J. et al. Science 333, 348–353 (2011).

    Article  CAS  Google Scholar 

  16. Johnson, D.B. et al. Nat. Chem. Biol. 7, 779–786 (2011).

    Article  CAS  Google Scholar 

  17. Khare, S.D. et al. Nat. Chem. Biol. 8, 294–300 (2012).

    Article  CAS  Google Scholar 

  18. Ieong, K.W., Pavlov, M.Y., Kwiatkowski, M., Forster, A.C. & Ehrenberg, M. J. Am. Chem. Soc. 134, 17955–17962 (2012).

    Article  CAS  Google Scholar 

  19. Ling, J., Reynolds, N. & Ibba, M. Annu. Rev. Microbiol. 63, 61–78 (2009).

    Article  CAS  Google Scholar 

  20. Richmond, M.H. Bacteriol. Rev. 26, 398–420 (1962).

    CAS  PubMed  PubMed Central  Google Scholar 

  21. Wang, Y.S., Fang, X., Wallace, A.L., Wu, B. & Liu, W.R. J. Am. Chem. Soc. 134, 2950–2953 (2012).

    Article  CAS  Google Scholar 

  22. Young, D.D. et al. Biochemistry 50, 1894–1900 (2011).

    Article  CAS  Google Scholar 

  23. Neumann, H., Wang, K., Davis, L., Garcia-Alai, M. & Chin, J.W. Nature 464, 441–444 (2010).

    Article  CAS  Google Scholar 

  24. Giegé, R., Sissler, M. & Florentz, C. Nucleic Acids Res. 26, 5017–5035 (1998).

    Article  Google Scholar 

  25. Su, D. et al. Nucleic Acids Res. 39, 4866–4874 (2011).

    Article  CAS  Google Scholar 

  26. Umehara, T. et al. FEBS Lett. 586, 729–733 (2012).

    Article  CAS  Google Scholar 

  27. Tanrikulu, I.C., Schmitt, E., Mechulam, Y., Goddard, W.A. III & Tirrell, D.A. Proc. Natl. Acad. Sci. USA 106, 15285–15290 (2009).

    Article  CAS  Google Scholar 

  28. Boniecki, M.T., Vu, M.T., Betha, A.K. & Martinis, S.A. Proc. Natl. Acad. Sci. USA 105, 19223–19228 (2008).

    Article  CAS  Google Scholar 

  29. Reynolds, N.M. et al. Proc. Natl. Acad. Sci. USA 107, 4063–4068 (2010).

    Article  CAS  Google Scholar 

  30. Ling, J. & Söll, D. Proc. Natl. Acad. Sci. USA 107, 4028–4033 (2010).

    Article  CAS  Google Scholar 

Download references


We are grateful to M. Englert, I. Heinemann, F. Isaacs and J. Rinehart for inspired discussions. Work in the authors' laboratory was supported by the Division of Chemical Sciences, Geosciences and Biosciences, Office of Basic Energy Sciences of the US Department of Energy (DE-FG02-98ER20311); the National Institute of General Medical Sciences (GM22854); DARPA contracts N66001-12-C-4020 and N66001-12-C-4211; and by the National Science Foundation (MCB-0950474).

Author information

Authors and Affiliations


Corresponding author

Correspondence to Dieter Söll.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Rights and permissions

Reprints and permissions

About this article

Cite this article

O'Donoghue, P., Ling, J., Wang, YS. et al. Upgrading protein synthesis for synthetic biology. Nat Chem Biol 9, 594–598 (2013).

Download citation

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing