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A chemocentric view of the natural product inventory

As the identification of previously undetected microbial biosynthetic pathways burgeons, there arises the question of how much new chemistry is yet to be found. This, in turn, devolves to: what kinds of biosynthetic enzymatic transformations are yet to be characterized?

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Figure 1: Oxygenases catalyzing key chemical steps in biosynthetic pathways.
Figure 2: Enzymes catalyzing complex cyclizations.
Figure 3: Polycyclic fungal alkaloid biosynthetic pathways.
Figure 4: Hybrid assembly lines.
Figure 5: Nonribosomal peptides can be cyclized in several modes and can have high affinity and specificity towards protein targets.

References

  1. 1

    Fischbach, M.A. & Walsh, C.T. Chem. Rev. 106, 3468–3496 (2006).

    CAS  Article  Google Scholar 

  2. 2

    Walsh, C.T. & Fischbach, M.A. J. Am. Chem. Soc. 132, 2469–2493 (2010).

    CAS  Article  Google Scholar 

  3. 3

    Klein, A.P., Anarat-Cappillino, G. & Sattely, E.S. Angew. Chem. 52, 13625–13628 (2013).

    CAS  Article  Google Scholar 

  4. 4

    Matsuda, Y., Wakimoto, T., Mori, T., Awakawa, T. & Abe, I. J. Am. Chem. Soc. 136, 15326–15336 (2014).

    CAS  Article  Google Scholar 

  5. 5

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

    Article  Google Scholar 

  6. 6

    Elshahawi, S.I., Shaaban, K.A., Kharel, M.K. & Thorson, J.S. Chem. Soc. Rev. doi:10.1039/C4CS00426D (2015).

  7. 7

    Fage, C.D. et al. Nat. Chem. Biol. 11, 256–258 (2015).

    CAS  Article  Google Scholar 

  8. 8

    Kim, H.J., Ruszczycky, M.W., Choi, S.H., Liu, Y.N. & Liu, H.W. Nature 473, 109–112 (2011).

    CAS  Article  Google Scholar 

  9. 9

    Bowers, A.A., Walsh, C.T. & Acker, M.G. J. Am. Chem. Soc. 132, 12182–12184 (2010).

    CAS  Article  Google Scholar 

  10. 10

    Wever, W.J. et al. J. Am. Chem. Soc. 137, 3494–3497 (2015).

    CAS  Article  Google Scholar 

  11. 11

    Tsunematsu, Y. et al. Nat. Chem. Biol. 9, 818–825 (2013).

    CAS  Article  Google Scholar 

  12. 12

    Xu, W., Gavia, D.J. & Tang, Y. Nat. Prod. Rep. 31, 1474–1487 (2014).

    CAS  Article  Google Scholar 

  13. 13

    Walsh, C.T. ACS Chem. Biol. 9, 2718–2728 (2014).

    CAS  Article  Google Scholar 

  14. 14

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

    CAS  Article  Google Scholar 

  15. 15

    Lin, H.C. et al. Angew. Chem. 54, 3004–3007 (2015).

    CAS  Article  Google Scholar 

  16. 16

    Walsh, C.T., Haynes, S.W., Ames, B.D., Gao, X. & Tang, Y. ACS Chem. Biol. 8, 1366–1382 (2013).

    CAS  Article  Google Scholar 

  17. 17

    Cociancich, S. et al. Nat. Chem. Biol. 11, 195–197 (2015).

    CAS  Article  Google Scholar 

  18. 18

    Baumann, S. et al. Angew. Chem. 53, 14605–14609 (2014).

    CAS  Article  Google Scholar 

  19. 19

    Walsh, C.T., O'Brien, R.V. & Khosla, C. Angew. Chem. 52, 7098–7124 (2013).

    CAS  Article  Google Scholar 

  20. 20

    Herkommer, D. et al. J. Am. Chem. Soc. 137, 4086–4089 (2015).

    CAS  Article  Google Scholar 

  21. 21

    Phillips, J.W. et al. Chem. Biol. 18, 955–965 (2011).

    CAS  Article  Google Scholar 

  22. 22

    Walsh, C.T. Science 303, 1805–1810 (2004).

    CAS  Article  Google Scholar 

  23. 23

    Brötz-Oesterhelt, H. et al. Nat. Med. 11, 1082–1087 (2005).

    Article  Google Scholar 

  24. 24

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

    CAS  Article  Google Scholar 

  25. 25

    Hamamoto, H. et al. Nat. Chem. Biol. 11, 127–133 (2015).

    CAS  Article  Google Scholar 

  26. 26

    Kling, A. et al. Science 348, 1106–1112 (2015).

    CAS  Article  Google Scholar 

  27. 27

    Arnison, P.G. et al. Nat. Prod. Rep. 30, 108–160 (2013).

    CAS  Article  Google Scholar 

  28. 28

    Hubbard, B.K. & Walsh, C.T. Angew. Chem. 42, 730–765 (2003).

    CAS  Article  Google Scholar 

  29. 29

    Sofia, H.J., Chen, G., Hetzler, B.G., Reyes-Spindola, J.F. & Miller, N.E. Nucleic Acids Res. 29, 1097–1106 (2001).

    CAS  Article  Google Scholar 

  30. 30

    Bauerle, M.R., Schwalm, E.L. & Booker, S.J. J. Biol. Chem. 290, 3995–4002 (2015).

    CAS  Article  Google Scholar 

  31. 31

    Seyedsayamdost, M.R., Wang, R., Kolter, R. & Clardy, J. J. Am. Chem. Soc. 136, 15150–15153 (2014).

    CAS  Article  Google Scholar 

  32. 32

    Xu, Y. et al. Proc. Natl. Acad. Sci. USA 111, 12354–12359 (2014).

    CAS  Article  Google Scholar 

  33. 33

    Zhu, X., Liu, J. & Zhang, W. Nat. Chem. Biol. 11, 115–120 (2015).

    CAS  Article  Google Scholar 

  34. 34

    Rui, Z. et al. Proc. Natl. Acad. Sci. USA 111, 18237–18242 (2014).

    CAS  Article  Google Scholar 

Download references

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Correspondence to Christopher T Walsh.

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Walsh, C. A chemocentric view of the natural product inventory. Nat Chem Biol 11, 620–624 (2015). https://doi.org/10.1038/nchembio.1894

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