Skip to main content
SpringerLink
Log in

A global assembly line for cyanobactins

  • Brief Communication
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Abstract

More than 100 cyclic peptides harboring heterocyclized residues are known from marine ascidians, sponges and different genera of cyanobacteria. Here, we report an assembly line responsible for the biosynthesis of these diverse peptides, now called cyanobactins, both in symbiotic and free-living cyanobacteria. By comparing five new cyanobactin biosynthetic clusters, we produced the prenylated antitumor preclinical candidate trunkamide in Escherichia coli culture using genetic engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: Cyanobactin pathways in cyanobacteria.
Figure 2: The tru pathway to patellins and trunkamide.

Similar content being viewed by others

Accession codes

Accessions

GenBank/EMBL/DDBJ

References

  1. Davidson, B.S. Chem. Rev. 93, 1771–1791 (1993).

    Article  CAS  Google Scholar 

  2. Schmidt, E.W. et al. Proc. Natl. Acad. Sci. USA 102, 7315–7320 (2005).

    CAS  PubMed  Google Scholar 

  3. Long, P.F., Dunlap, W.C., Battershill, C.N. & Jaspars, M. ChemBioChem 6, 1760–1765 (2005).

    Article  CAS  Google Scholar 

  4. Ireland, C.M., Durso, A.R., Newman, R.A. & Hacker, M.P. J. Org. Chem. 47, 1807–1811 (1982).

    Article  CAS  Google Scholar 

  5. Degnan, B.M. et al. J. Med. Chem. 32, 1349–1354 (1989).

    Article  CAS  Google Scholar 

  6. Donia, M.S. et al. Nat. Chem. Biol. 2, 729–735 (2006).

    Article  CAS  Google Scholar 

  7. Sudek, S., Haygood, M.G., Youssef, D.T. & Schmidt, E.W. Appl. Environ. Microbiol. 72, 4382–4387 (2006).

    Article  CAS  Google Scholar 

  8. Li, Y.-M., Milne, J.C., Madison, L.L., Kolter, R. & Walsh, C.T. Science 274, 1188–1193 (1996).

    Article  CAS  Google Scholar 

  9. Milne, B.F., Long, P.F., Starcevic, A., Hranueli, D. & Jaspars, M. Org. Biomol. Chem. 4, 631–638 (2006).

    Article  CAS  Google Scholar 

  10. Carroll, A.R. et al. Aust. J. Chem. 49, 659–667 (1996).

    Article  CAS  Google Scholar 

  11. Zabriskie, T.M., Foster, M.P., Stout, T.J., Clardy, J. & Ireland, C.M. J. Am. Chem. Soc. 112, 8080–8084 (1990).

    Article  CAS  Google Scholar 

  12. Salvatella, X., Caba, J.M., Albericio, F. & Giralt, E. J. Org. Chem. 68, 211–215 (2003).

    Article  CAS  Google Scholar 

  13. Tan, L.T. Phytochemistry 68, 954–979 (2007).

    Article  CAS  Google Scholar 

  14. Banker, R. & Carmeli, S. J. Nat. Prod. 61, 1248–1251 (1998).

    Article  CAS  Google Scholar 

  15. Ziemert, N. et al. Appl. Environ. Microbiol. 74, 1791–1797 (2008).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by grants from the US National Institutes of Health (GM071425) and the National Science Foundation (EF-0412226). We thank C. Ireland (University of Utah), the University of the South Pacific, the Solomon Islands and the Republic of the Fiji Islands for providing opportunities to collect marine animal samples. S. Meo (University of the South Pacific) aided with the collection of L. patella in Fiji. S. Carmeli (Tel-Aviv University) provided the N. spongiaeforme culture. J.G. Muller and T. Bugni (University of Utah) helped with mass spectrometry experiments. A. Bird and D. Winge (University of Utah) helped with yeast recombination. C. Ireland provided ascidian photos.

Author information

Authors and Affiliations

  1. Department of Medicinal Chemistry, University of Utah, 30 South 2000 East, Room 201, Salt Lake City, 84112, Utah, USA

    Mohamed S Donia & Eric W Schmidt

  2. Department of Microbiology & Immunology, Institute for Genome Sciences, University of Maryland School of Medicine, 20 Penn Street, Baltimore, 21201, Maryland, USA

    Jacques Ravel

Authors
  1. Mohamed S Donia
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jacques Ravel
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Eric W Schmidt
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.S.D. performed all experiments and wrote the manuscript; J.R. did most of the sequencing and helped in editing the manuscript; E.W.S. did the original collection and processing of the marine samples, directed the project and helped write and edit the manuscript.

Corresponding author

Correspondence to Eric W Schmidt.

Ethics declarations

Competing interests

E.W.S. is an inventor on a patent application at the University of Utah for the practical application of cyclic peptide library synthesis. Some of the claims are supported by this work.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–6, Supplementary Tables 1 and 2, and Supplementary Methods (PDF 9093 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Donia, M., Ravel, J. & Schmidt, E. A global assembly line for cyanobactins. Nat Chem Biol 4, 341–343 (2008). https://doi.org/10.1038/nchembio.84

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio.84

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation