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

Nature Chemical Biology volume 13, pages 836–838 (2017)Cite this article

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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.

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Figure 1: Select Piz-containing natural products and their biosynthetic gene clusters.
Figure 2: KtzT catalyzes N–N bond formation to give piperazate.
Figure 3: KtzT is a heme-dependent enzyme.

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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.

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Authors and 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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  1. Yi-Ling Du
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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.

Corresponding author

Correspondence to Katherine S Ryan.

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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.

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Supplementary Results, Supplementary Table 1 and Supplementary Figures 1–14 (PDF 4481 kb)

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Du, YL., He, HY., Higgins, M. et al. A heme-dependent enzyme forms the nitrogen–nitrogen bond in piperazate. Nat Chem Biol 13, 836–838 (2017). https://doi.org/10.1038/nchembio.2411

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