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.

Biochemistry

Positive and radical

Nature volume 496, pages 34–35 (2013)Cite this article

Subjects

Biosynthesis of the antibiotic fosfomycin ends with the formation of an 'epoxide' ring structure. The epoxide is suggested to form from a cationic intermediate, rather than from a free radical. See Letter p.114

Most enzymes described in biochemistry textbooks catalyse reactions that involve the movement of two electrons. In such chemistry, a reagent (the nucleophile) with a reactive electron pair interacts with a partner (the electrophile) that is electron-deficient. Carbanions and carbocations are examples of carbon-based nucleophiles and electrophiles, respectively. In nature, reactions that cannot be easily accomplished by two-electron chemistry are often mediated by metalloenzymes that catalyse single-electron chemistry. In organic substrates, such reactions are typically thought to involve radicals (in which a carbon atom has one unpaired electron), but detecting these intermediates has been challenging because they are highly reactive. The non-haem iron-dependent enzymes form a large class of such metalloenzymes1. On page 114 of this issue, Chang et al.2 provide data suggesting that at least one enzyme in this class uses both a carbon-centred radical and a carbocation as intermediates during the biosynthesis of fosfomycin, an antibiotic used in clinical settings and produced by several bacterial strains.

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

Access options

Rent or buy this article

Get just this article for as long as you need it

$39.95

Learn more

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

Figure 1: Reactions catalysed by the (S)-2-hydroxypropylphosphonate epoxidase (HppE) enzyme.
Figure 2: Proposed mechanisms of HppE-catalysed reactions.

References

  1. Kovaleva, E. G. & Lipscomb, J. D. Nature Chem. Biol. 4, 186–193 (2008).

    Article  CAS  Google Scholar 

  2. Chang, W. et al. Nature 496, 114–118 (2013).

    Article  ADS  CAS  Google Scholar 

  3. Hammerschmidt, F. J. Chem. Soc. Perkin Trans. 1, 1993–1996 (1991).

    Article  Google Scholar 

  4. Liu, P. et al. J. Am. Chem. Soc. 123, 4619–4620 (2001).

    Article  CAS  Google Scholar 

  5. Huang, H. et al. J. Am. Chem. Soc. 134, 16171–16174 (2012).

    Article  CAS  Google Scholar 

  6. Higgins, L. J., Yan, F., Liu, P., Liu, H. W. & Drennan, C. L. Nature 437, 838–844 (2005).

    Article  ADS  CAS  Google Scholar 

  7. Groves, J. T. J. Inorg. Biochem. 100, 434–447 (2006).

    Article  CAS  Google Scholar 

  8. Cicchillo, R. M. et al. Nature 459, 871–874 (2009).

    Article  ADS  CAS  Google Scholar 

  9. Metcalf, W. W. et al. Science 337, 1104–1107 (2012).

    Article  ADS  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. and in the Department of Chemistry and Howard Hughes Medical Institute, Spencer C. Peck and Wilfred A. van der Donk are at the Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois 61801, USA, University of Illinois at Urbana-Champaign.,

    Spencer C. Peck & Wilfred A. van der Donk

Authors
  1. Spencer C. Peck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wilfred A. van der Donk
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wilfred A. van der Donk.

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Peck, S., van der Donk, W. Positive and radical. Nature 496, 34–35 (2013). https://doi.org/10.1038/496034a

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/496034a

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