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A new family of iron-dependent halogenases acts on freestanding substrates

Nature Chemical Biology volume 10, pages 921–923 (2014)Cite this article

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Abstract

Regio- and stereospecific incorporation of a halogen atom to an unactivated sp3 carbon in a freestanding molecule is a challenging transformation that is currently missing in the inventory of enzyme-mediated reactions. Here we report what is to our knowledge the first example of a nonheme iron enzyme (WelO5) in the welwitindolinone biosynthetic pathway that can monochlorinate an aliphatic carbon in 12-epi-fischerindole U and 12-epi-hapalindole C, substrates that are free from peptidyl or acyl carrier protein.

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Figure 1: Selected chlorinated and deschlorinated pairs of hapalindole-type molecules from two distinct stigonematalean cyanobacteria.
Figure 2: In vitro characterization of WelO5 and its mutant.

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References

  1. Gribble, G.W. Prog. Chem. Org. Nat. Prod. 91, 1–613 (2010).

    CAS  Google Scholar 

  2. Harris, C.M., Kannan, R., Kopecka, H. & Harris, T.M. J. Am. Chem. Soc. 107, 6652–6658 (1985).

    Article  CAS  Google Scholar 

  3. Williams, P.G. et al. J. Org. Chem. 70, 6196–6203 (2005).

    Article  CAS  Google Scholar 

  4. Insall, R. & Kay, R.R. EMBO J. 9, 3323–3328 (1990).

    Article  CAS  Google Scholar 

  5. Vaillancourt, F.H., Yeh, E., Vosburg, D.A., Garneau-Tsodikova, S. & Walsh, C.T. Chem. Rev. 106, 3364–3378 (2006).

    Article  CAS  Google Scholar 

  6. Carter-Franklin, J.N. & Butler, A. J. Am. Chem. Soc. 126, 15060–15066 (2004).

    Article  CAS  Google Scholar 

  7. Bernhardt, P., Okino, T., Winter, J.M., Miyanaga, A. & Moore, B.S. J. Am. Chem. Soc. 133, 4268–4270 (2011).

    Article  CAS  Google Scholar 

  8. Kirner, S. et al. J. Bacteriol. 180, 1939–1943 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  9. Neumann, C.S., Walsh, C.T. & Kay, R.R. Proc. Natl. Acad. Sci. USA 107, 5798–5803 (2010).

    Article  CAS  Google Scholar 

  10. Podust, L.M. & Sherman, D.H. Nat. Prod. Rep. 29, 1251–1266 (2012).

    Article  CAS  Google Scholar 

  11. Bhat, V., Dave, A., MacKay, J.A. & Rawal, V.H. Alkaloids Chem. Biol. 73, 65–160 (2014).

    Article  CAS  Google Scholar 

  12. Park, A., Moore, R.E. & Patterson, G.M.L. Tetrahedr. Lett. 33, 3257–3260 (1992).

    Article  CAS  Google Scholar 

  13. Stratmann, K. et al. J. Am. Chem. Soc. 116, 9935–9942 (1994).

    Article  CAS  Google Scholar 

  14. Hillwig, M.L., Zhu, Q. & Liu, X. ACS Chem. Biol. 9, 372–377 (2014).

    Article  CAS  Google Scholar 

  15. Hillwig, M.L. et al. ChemBioChem 15, 665–669 (2014).

    Article  CAS  Google Scholar 

  16. Vaillancourt, F.H., Yin, J. & Walsh, C.T. Proc. Natl. Acad. Sci. USA 102, 10111–10116 (2005).

    Article  CAS  Google Scholar 

  17. Vaillancourt, F.H., Yeh, E., Vosburg, D.A., O'Connor, S.E. & Walsh, C.T. Nature 436, 1191–1194 (2005).

    Article  CAS  Google Scholar 

  18. Galonić, D.P., Vaillancourt, F.H. & Walsh, C.T. J. Am. Chem. Soc. 128, 3900–3901 (2006).

    Article  Google Scholar 

  19. Ueki, M. et al. Chem. Biol. 13, 1183–1191 (2006).

    Article  CAS  Google Scholar 

  20. Gu, L. et al. Nature 459, 731–735 (2009).

    Article  CAS  Google Scholar 

  21. Matthews, M.L. et al. Proc. Natl. Acad. Sci. USA 106, 17723–17728 (2009).

    Article  CAS  Google Scholar 

  22. Matthews, M.L. et al. Biochemistry 48, 4331–4343 (2009).

    Article  CAS  Google Scholar 

  23. Galonić, D.P., Barr, E.W., Walsh, C.T., Bollinger, J.M. Jr. & Krebs, C. Nat. Chem. Biol. 3, 113–116 (2007).

    Article  Google Scholar 

  24. Khare, D. et al. Proc. Natl. Acad. Sci. USA 107, 14099–14104 (2010).

    Article  CAS  Google Scholar 

  25. Blasiak, L.C., Vaillancourt, F.H., Walsh, C.T. & Drennan, C.L. Nature 440, 368–371 (2006).

    Article  CAS  Google Scholar 

  26. Moore, R.E. et al. J. Org. Chem. 52, 1036–1043 (1987).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by University of Pittsburgh–Department of Chemistry startup fund.

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Authors and Affiliations

  1. Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania, USA

    Matthew L Hillwig & Xinyu Liu

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  1. Matthew L Hillwig
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  2. Xinyu Liu
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Contributions

M.L.H. and X.L. designed the study. M.L.H. performed all experiments. M.L.H. and X.L. analyzed the data. X.L. wrote the manuscript with input from M.L.H.

Corresponding author

Correspondence to Xinyu Liu.

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The authors declare no competing financial interests.

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Supplementary Results and Supplementary Figures 1–16. (PDF 3946 kb)

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Hillwig, M., Liu, X. A new family of iron-dependent halogenases acts on freestanding substrates. Nat Chem Biol 10, 921–923 (2014). https://doi.org/10.1038/nchembio.1625

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