A global assembly line for cyanobactins (original) (raw)

Nature Chemical Biology volume 4, pages 341–343 (2008)Cite this article

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, access via your institution

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Additional access options:

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
    You can also search for this author inPubMed Google Scholar
  2. Jacques Ravel
    You can also search for this author inPubMed Google Scholar
  3. Eric W Schmidt
    You can also search for this author inPubMed 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 toEric 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

Rights 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

This article is cited by

Editorial Summary