Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Brief Communication
  • Published:

Structure and specificity of a permissive bacterial C-prenyltransferase


This study highlights the biochemical and structural characterization of the L-tryptophan C6 C-prenyltransferase (C-PT) PriB from Streptomyces sp. RM-5-8. PriB was found to be uniquely permissive to a diverse array of prenyl donors and acceptors including daptomycin. Two additional PTs also produced novel prenylated daptomycins with improved antibacterial activities over the parent drug.

This is a preview of subscription content, access via your institution

Access options

Buy this article

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

Figure 1: PriB discovery and permissiveness of PriB and other indole PTs.
Figure 2: Prenylated daptomycins (DAPs) and the crystal structure of PriB.

Similar content being viewed by others

Accession codes

Primary accessions

NCBI Reference Sequence

Protein Data Bank


  1. Walsh, C.T. Nat. Chem. Biol. 11, 620–624 (2015).

    Article  CAS  Google Scholar 

  2. Tibrewal, N. & Tang, Y. Annu. Rev. Chem. Biomol. Eng. 5, 347–366 (2014).

    Article  CAS  Google Scholar 

  3. Gantt, R.W., Peltier-Pain, P. & Thorson, J.S. Nat. Prod. Rep. 28, 1811–1853 (2011).

    Article  CAS  Google Scholar 

  4. Elshahawi, S.I. et al. Proc. Natl. Acad. Sci. USA 110, E295–E304 (2013).

    Article  CAS  Google Scholar 

  5. Ling, L.L. et al. Nature 517, 455–459 (2015).

    Article  CAS  Google Scholar 

  6. Donia, M.S. & Fischbach, M.A. Science 349, 1254766 (2015).

    Article  Google Scholar 

  7. Carr, G. et al. Org. Lett. 14, 2822–2825 (2012).

    Article  CAS  Google Scholar 

  8. Wang, X. et al. Org. Lett. 17, 2796–2799 (2015).

    Article  CAS  Google Scholar 

  9. Fan, A., Winkelblech, J. & Li, S.-M. Appl. Microbiol. Biotechnol. 99, 7399–7415 (2015).

    Article  CAS  Google Scholar 

  10. Rudolf, J.D., Wang, H. & Poulter, C.D. J. Am. Chem. Soc. 135, 1895–1902 (2013).

    Article  CAS  Google Scholar 

  11. Takahashi, S. et al. J. Bacteriol. 192, 2839–2851 (2010).

    Article  CAS  Google Scholar 

  12. Winkelblech, J. & Li, S.M. ChemBioChem 15, 1030–1039 (2014).

    Article  CAS  Google Scholar 

  13. Rudolf, J.D. & Poulter, C.D. ACS Chem. Biol. 8, 2707–2714 (2013).

    Article  CAS  Google Scholar 

  14. Mori, T. et al. Nat. Commun. 7, 10849 (2016).

    Article  CAS  Google Scholar 

  15. Subramanian, T., Liu, S., Troutman, J.M., Andres, D.A. & Spielmann, H.P. ChemBioChem 9, 2872–2882 (2008).

    Article  CAS  Google Scholar 

  16. Eisenstein, B.I., Oleson, F.B. Jr. & Baltz, R.H. Clin. Infect. Dis. 50 (Suppl. 1): S10–S15 (2010).

    Article  CAS  Google Scholar 

  17. Unsöld, I.A. & Li, S.-M. Microbiology 151, 1499–1505 (2005).

    Article  Google Scholar 

  18. Mahmoodi, N. & Tanner, M.E. ChemBioChem 14, 2029–2037 (2013).

    Article  CAS  Google Scholar 

  19. Yin, N. et al. J. Med. Chem. 58, 5137–5142 (2015).

    Article  CAS  Google Scholar 

  20. Kuzuyama, T., Noel, J.P. & Richard, S.B. Nature 435, 983–987 (2005).

    Article  CAS  Google Scholar 

  21. Bonitz, T., Alva, V., Saleh, O., Lupas, A.N. & Heide, L. PLoS One 6, e27336 (2011).

    Article  CAS  Google Scholar 

  22. Tanner, M.E. Nat. Prod. Rep. 32, 88–101 (2015).

    Article  CAS  Google Scholar 

  23. Williams, G.J., Zhang, C. & Thorson, J.S. Nat. Chem. Biol. 3, 657–662 (2007).

    Article  CAS  Google Scholar 

  24. Nobeli, I., Favia, A.D. & Thornton, J.M. Nat. Biotechnol. 27, 157–167 (2009).

    Article  CAS  Google Scholar 

  25. Feng, Y. et al. J. Am. Chem. Soc. 137, 10160–10163 (2015).

    Article  CAS  Google Scholar 

  26. Chehade, K.A.H. et al. J. Am. Chem. Soc. 124, 8206–8219 (2002).

    Article  CAS  Google Scholar 

  27. Subramanian, T., Wang, Z., Troutman, J.M., Andres, D.A. & Spielmann, H.P. Org. Lett. 7, 2109–2112 (2005).

    Article  CAS  Google Scholar 

  28. Kearse, M. et al. Bioinformatics 28, 1647–1649 (2012).

    Article  Google Scholar 

  29. Debono, M. et al. J. Antibiot. (Tokyo) 41, 1093–1105 (1988).

    Article  CAS  Google Scholar 

  30. Shaaban, K.A. et al. J. Nat. Prod. 78, 1723–1729 (2015).

    Article  CAS  Google Scholar 

  31. Kabsch, W. Acta Crystallogr. D Biol. Crystallogr. 66, 125–132 (2010).

    Article  CAS  Google Scholar 

  32. Collaborative Computational Project, Number 4. Acta Crystallogr. D Biol. Crystallogr. 50, 760–763 (1994).

  33. Adams, P.D. et al. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

    Article  CAS  Google Scholar 

  34. Emsley, P., Lohkamp, B., Scott, W.G. & Cowtan, K. Acta Crystallogr. D Biol. Crystallogr. 66, 486–501 (2010).

    Article  CAS  Google Scholar 

  35. Chen, V.B. et al. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

    Article  CAS  Google Scholar 

Download references


This work was supported by NIH grants R37 AI52188 and R01 CA203257 (J.S.T.), U01 GM098248 (G.N.P.) and NCATS (UL1TR001998). Daptomycin (Cubicin) was generously provided by Merck. We are grateful to J. Rohr, S. Van Lanen and J. Chappell (College of Pharmacy, University of Kentucky) for helpful discussion and facilitating access to shared equipment and/or reagents. We thank the University of Kentucky Mass Spectrometry Facility for the HR–ESI–MS support. This research also used resources of the Advanced Photon Source, a US Department of Energy (DOE) Office of Science user facility operated by Argonne National Laboratory (DE-AC02-06CH11357). Use of the Lilly Research Laboratories Collaborative Access Team (LRL-CAT) beamline at Sector 31 of the Advanced Photon Source was provided by Eli Lilly and Company.

Author information

Authors and Affiliations



S.I.E. and H.C. contributed to the experimental design and execution and manuscript preparation; K.A.S. and L.V.P. contributed to experimental design and execution; T.S. and H.P.S. contributed experimental reagents and consultation; M.L.F. contributed to experimental design and execution and provided key consultation; G.N.P. and J.S.T. contributed to the experimental design, project oversight and manuscript preparation; S.S. contributed to the experimental design and execution, project oversight and manuscript preparation.

Corresponding authors

Correspondence to George N Phillips Jr, Jon S Thorson or Shanteri Singh.

Ethics declarations

Competing interests

J.S.T. is a cofounder of Centrose (Madison, Wisonsin, USA).

Supplementary information

Supplementary Text and Figures

Supplementary Results, Supplementary Figures 1–28 and Supplementary Tables 1–11. (PDF 2642 kb)

Supplementary Note

NMR and mass spectral data supporting the structural elucidation of compounds 1, 66, 67, 68, 69, 70 and the prenylated analogs of 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65. (PDF 15278 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Elshahawi, S., Cao, H., Shaaban, K. et al. Structure and specificity of a permissive bacterial C-prenyltransferase. Nat Chem Biol 13, 366–368 (2017).

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI:

This article is cited by


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing