Brief Communication | Published:

A heme-dependent enzyme forms the nitrogen–nitrogen bond in piperazate

Nature Chemical Biology volume 13, pages 836838 (2017) | Download Citation

Abstract

Molecules containing a nitrogen–nitrogen (N–N) linkage have a variety of structures and biological activities; however, no enzyme has yet been demonstrated to catalyze N–N bond formation in an organic molecule. Here we report that the heme-dependent enzyme KtzT from Kutzneria sp. 744 catalyzes N–N bond formation in the biosynthesis of piperazate, a building block for nonribosomal peptides.

  • Compound

    L-ornithine

  • Compound

    L-N5-OH-ornithine

  • Compound

    L-piperazic acid

  • Compound

    D-N5-OH-ornithine

  • Compound

    L-N4-OH-2,4-diaminobutyrate

  • Compound

    L-N6-OH-lysine

  • Compound

    pyrazolidine-3-carboxylic acid

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Acknowledgements

We thank L.D. Eltis and E. Kuatsjah for use of an oxygen electrode. We are grateful to C. Drennan (MIT) for provision of pET28a-ktzI. This work was supported by a Discovery Grant from the Natural Sciences and Engineering Research Council of Canada. Y.-L.D. and M.A.H. were supported by Michael Smith Foundation for Health Research Trainee Awards, and K.S.R. is a Canadian Institutes of Health Research New Investigator.

Author information

Affiliations

  1. Institute of Pharmaceutical Biotechnology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China.

    • Yi-Ling Du
  2. Department of Chemistry, The University of British Columbia, Vancouver, BC, Canada.

    • Yi-Ling Du
    • , Hai-Yan He
    • , Melanie A Higgins
    •  & Katherine S Ryan

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Contributions

Y.-L.D. designed the study, performed experiments, analyzed data, and wrote the manuscript. H.-Y.H. directed synthetic work. M.A.H. carried out gel-filtration studies. K.S.R. designed the study and wrote the manuscript.

Competing interests

Y.-L.D. and K.S.R. are on a provisional patent application, filed through the University of British Columbia (at which K.S.R. is employed), that is based on the results described here.

Corresponding author

Correspondence to Katherine S Ryan.

Supplementary information

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    Supplementary Text and Figures

    Supplementary Results, Supplementary Table 1 and Supplementary Figures 1–14

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DOI

https://doi.org/10.1038/nchembio.2411

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