Skip to main content

Thank you for visiting nature.com. 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.

PROTEIN EVOLUTION

Enzymes emerge by upcycling

Nature Chemical Biology volume 14, pages 526–527 (2018)Cite this article

Subjects

Catalytic activity is a critical protein function, but its natural evolution has never been observed. Researchers have now revealed the mutations and biochemical mechanisms by which two ancient nonenzymatic proteins acquired catalytic activity.

Enzyme activity involves many amino acids in a protein, both inside and outside the active site. How does evolution put together such complicated machines? In this issue, two studies have answered this question by dissecting the natural evolution of two enzymes from nonenzymatic ancestors1,2. Although these enzymes catalyze different reactions, their evolutionary trajectories exhibit similar characteristics. In both cases, key residues involved in catalysis were present in the binding pocket before catalysis itself evolved. A collection of mutations then reshaped the pockets around those residues, upcycling a pre-existing binding site into a weak active site. This nascent activity was then further optimized by mutations that functioned to align the reactants and limit molecular motions that interfered with catalysis. The striking similarity of the results for these two enzymes—which, incidentally, also parallels current approaches in enzyme engineering3—suggests that this is a common mechanism by which new enzyme activities evolve.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Fig. 1: Enzyme activity evolved by activating existing residues and quenching dynamics.

References

  1. Clifton, B. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-018-0043-2 (2018).

  2. Kaltenbach, M. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-018-0042-3 (2018).

  3. Mak, W. S. & Siegel, J. B. Curr. Opin. Struct. Biol. 27, 87–94 (2014).

    Article  CAS  PubMed  Google Scholar 

  4. Pauling, L. & Zuckerkandl, E. Acta Chem. Scand. 17, S9–S16 (1963).

    Article  CAS  Google Scholar 

  5. Harms, M. J. & Thornton, J. W. Curr. Opin. Struct. Biol. 20, 360–366 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Steindel, P. A., Chen, E. H., Wirth, J. D. & Theobald, D. L. Protein Sci. 25, 1319–1331 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Anderson, D. P. et al. eLife 5, e10147 (2016).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Lynch, V. J., May, G. & Wagner, G. P. Nature 480, 383–386 (2011).

    Article  CAS  PubMed  Google Scholar 

  9. Natarajan, C. et al. Science 354, 336–339 (2016).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Tzul, F. O., Vasilchuk, D. & Makhatadze, G. I. Proc. Natl. Acad. Sci. USA 114, E1627–E1632 (2017).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Molecular Biology and Chemistry and Biochemistry Department, University of Oregon, Eugene, OR, USA

    Michael J. Harms

Authors
  1. Michael J. Harms
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Michael J. Harms.

Ethics declarations

Competing interests

The author declares no competing interests.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Harms, M.J. Enzymes emerge by upcycling. Nat Chem Biol 14, 526–527 (2018). https://doi.org/10.1038/s41589-018-0064-x

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41589-018-0064-x

Search

Advanced search

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