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ENZYMOLOGY

Flavin doesn’t put all oxygens in one basket

Nature Chemical Biology volume 16, pages 485–486 (2020)Cite this article

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Oxygen activation mechanisms catalyzed by flavin cofactors are established for electron transfer (oxidases) and C4a covalent flavin–oxygen adduct formation (oxygen-inserting monooxygenases). A new paradigm for oxygen insertion involving a flavin-N5-aminoperoxide intermediate has now been discovered in select flavin-dependent monooxygenases.

Flavins are intrinsically versatile. As free cofactors and during biological catalysis, they engage in a wide range of chemical reactions including long-range electron transfer, oxygen activation, photochemistry and reductive chemistry3. Despite a long history for flavin chemistry, unprecedented reactions continue to emerge. Notable recent discoveries include flavin prenylations that support enzyme-catalyzed (de)carboxylation4; photochemical activation of flavin for decarboxylation5 and stereoselective cyclizations6; formation of superoxidized flavin N5-oxides for the 4-electron oxidation of polyketides7 and flavin N5-centred C1 transfer reactions8. This catalytic and chemical versatility of flavin expands the utility of flavoenzymes as (photo)biocatalysts, broadening the reaction types available to biocatalysis toolkits. It also extends the capabilities of natural enzymes to engage in a wide range of cellular transformations, including light emission and light-dependent signaling9,10. Further surprises will no doubt come to light to illustrate yet more chemical versatility, especially as we continue to discover new flavoenzymes and engineer them toward novel function. That selected flavoproteins can use a flavin-N5-aminoperoxide adduct for monooxygenation is especially noteworthy. This finding breaks with dogma; flavoprotein monooxygenase reactions were inferred to progress exclusively through a covalent flavin-C4a-(hydro)peroxide intermediate prior to this discovery.

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Fig. 1: Schematic overview of the flavin mediated O2-reduction process.

References

  1. Romero, E., Gómez Castellanos, J. R., Gadda, G., Fraaije, M. W. & Mattevi, A. Chem. Rev. 118, 1742–1769 (2018).

    Article  CAS  Google Scholar 

  2. Matthews, A. et al. Nat. Chem. Biol. https://doi.org/10.1038/s41589-020-0476-2 (2020).

    Article  PubMed  Google Scholar 

  3. Leys, D. & Scrutton, N. S. Curr. Opin. Struct. Biol. 41, 19–26 (2016).

    Article  CAS  Google Scholar 

  4. Payne, K. A. P. et al. Nature 522, 497–501 (2015).

    Article  CAS  Google Scholar 

  5. Sorigué, D. et al. Science 357, 903–907 (2017).

    Article  Google Scholar 

  6. Black, M. J. et al. Nat. Chem. 12, 71–75 (2020).

    Article  Google Scholar 

  7. Teufel, R. et al. Nature 503, 552–556 (2013).

    Article  CAS  Google Scholar 

  8. Mishanina, T. V. et al. Science 351, 507–510 (2016).

    Article  CAS  Google Scholar 

  9. Conrad, K. S., Manahan, C. C. & Crane, B. R. Nat. Chem. Biol. 10, 801–809 (2014).

    Article  CAS  Google Scholar 

  10. Kutta, R. J., Archipowa, N. & Scrutton, N. S. Phys. Chem. Chem. Phys. 20, 28767–28776 (2018).

    Article  CAS  Google Scholar 

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  1. Manchester Institute of Biotechnology and Department of Chemistry, School of Natural Sciences, The University of Manchester, Manchester, UK

    David Leys & Nigel S. Scrutton

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  1. David Leys
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  2. Nigel S. Scrutton
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Correspondence to David Leys or Nigel S. Scrutton.

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Leys, D., Scrutton, N.S. Flavin doesn’t put all oxygens in one basket. Nat Chem Biol 16, 485–486 (2020). https://doi.org/10.1038/s41589-020-0523-z

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