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A nitrous acid biosynthetic pathway for diazo group formation in bacteria

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Abstract

Although some diazo compounds have bioactivities of medicinal interest, little is known about diazo group formation in nature. Here we describe an unprecedented nitrous acid biosynthetic pathway responsible for the formation of a diazo group in the biosynthesis of the ortho-diazoquinone secondary metabolite cremeomycin in Streptomyces cremeus. This finding provides important insights into the biosynthetic pathways not only for diazo compounds but also for other naturally occurring compounds containing nitrogen-nitrogen bonds.

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Figure 1: Organization of the cremeomycin biosynthetic gene cluster and in vivo analysis of the cre pathway.
Figure 2: Proposed cremeomycin biosynthetic pathway and in vitro analysis of CreE and CreD.

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Acknowledgements

We thank A. Luzhetskyy (Helmholtz Institute for Pharmaceutical Research Saarland), H. Onaka (University of Tokyo) and Y. Zhang (Gene Bridges) for providing pKGLP2, pTOYAMAcos and GB05dir, respectively. This research was supported in part by a funding program for next-generation world-leading researchers from the Bureau of Science, Technology and Innovation Policy, Cabinet Office, Government of Japan (GS006 to Y.O.), Grant-in-Aid for Young Scientists (B) (25850048 to Y.K.) and NC-CARP project from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT) (to Y.K. and Y.O.).

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Authors and Affiliations

  1. Department of Biotechnology, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan

    Yoshinori Sugai, Yohei Katsuyama & Yasuo Ohnishi

Authors
  1. Yoshinori Sugai
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  2. Yohei Katsuyama
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  3. Yasuo Ohnishi
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Contributions

Y.S. designed the study, performed experiments and wrote the manuscript. Y.K. designed the study, analyzed the data and wrote the manuscript. Y.O. directed the research, analyzed the data and wrote the manuscript.

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Correspondence to Yasuo Ohnishi.

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The authors declare no competing financial interests.

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Supplementary Results, Supplementary Tables 1 and 2 and Supplementary Figures 1–26. (PDF 9033 kb)

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Sugai, Y., Katsuyama, Y. & Ohnishi, Y. A nitrous acid biosynthetic pathway for diazo group formation in bacteria. Nat Chem Biol 12, 73–75 (2016). https://doi.org/10.1038/nchembio.1991

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