Skip to main content
SpringerLink
Log in

Evolving biosynthetic tangos negotiate mechanistic landscapes

  • Commentary
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Abstract

The dependence of polyketide synthase and terpene cyclase mechanistic adaptation on the chemistry of their oligomeric substrates illuminates a convergent evolutionary strategy for shaping cyclization in these otherwise disparate reactions. Evolution of these enzyme families relies on rhythmic tangos, in which the enzymes and substrates together determine product outcome by negotiating decision networks governing intrinsic and induced chemical reactivities.

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: Metabolic diversity via divergent intramolecular cyclization.
Figure 2: Convergent features of 'uber-adaptable' cyclases and their oligomeric substrates.
Figure 3: Biosynthetic tangos in the shade of a branching metabolic diversification tree.

Rebecca Henretta

Figure 4: Comparison of postcyclization reactions in the SC (left) and PKS III (right) 'reaction chambers'.

References

  1. Fischbach, M.A. & Clardy, J. Nat. Chem. Biol. 3, 353–355 (2007).

    Article  CAS  Google Scholar 

  2. Christianson, D.W. Chem. Rev. 106, 3412–3442 (2006).

    Article  CAS  Google Scholar 

  3. Austin, M.B. & Noel, J.P. Nat. Prod. Rep. 20, 79–110 (2003).

    Article  CAS  Google Scholar 

  4. Bomati, E.K., Austin, M.B., Bowman, M.E., Dixon, R.A. & Noel, J.P. J. Biol. Chem. 280, 30496–30503 (2005).

    Article  CAS  Google Scholar 

  5. Deguerry, F. et al. Arch. Biochem. Biophys. 454, 123–136 (2006).

    Article  CAS  Google Scholar 

  6. Mercke, P., Crock, J., Croteau, R. & Brodelius, P.E. Arch. Biochem. Biophys. 369, 213–222 (1999).

    Article  CAS  Google Scholar 

  7. Ferrer, J.L., Jez, J.M., Bowman, M.E., Dixon, R.A. & Noel, J.P. Nat. Struct. Biol. 6, 775–784 (1999).

    Article  CAS  Google Scholar 

  8. Starks, C.M., Back, K., Chappell, J. & Noel, J.P. Science 277, 1815–1820 (1997).

    Article  CAS  Google Scholar 

  9. Cane, D.E. Acc. Chem. Res. 18, 220–226 (1985).

    Article  CAS  Google Scholar 

  10. Jez, J.M. et al. Chem. Biol. 7, 919–930 (2000).

    Article  CAS  Google Scholar 

  11. Yoshikuni, Y., Ferrin, T.E. & Keasling, J.D. Nature 440, 1078–1082 (2006).

    Article  CAS  Google Scholar 

  12. Greenhagen, B.T., O'Maille, P.E., Noel, J.P. & Chappell, J. Proc. Natl. Acad. Sci. USA 103, 9826–9831 (2006).

    Article  CAS  Google Scholar 

  13. Austin, M.B., Bowman, M.E., Ferrer, J.L., Schröder, J. & Noel, J.P. Chem. Biol. 11, 1179–1194 (2004).

    Article  CAS  Google Scholar 

  14. Austin, M.B. et al. J. Biol. Chem. 279, 45162–45174 (2004).

    Article  CAS  Google Scholar 

  15. Austin, M.B. & Noel, J.P. in ACS Symposium Series 955, Polyketides: Biosynthesis, Biological Activities, and Genetic Engineering (eds. Rimando, A.M. & Baerson, S.R.) 185–197 (American Chemical Society, Washington DC, 2007).

    Book  Google Scholar 

  16. Wang, K. & Ohnuma, S. Trends Biochem. Sci. 24, 445–451 (1999).

    Article  CAS  Google Scholar 

  17. Umeno, D., Tobias, A.V. & Arnold, F.H. Microbiol. Mol. Biol. Rev. 69, 51–78 (2005).

    Article  CAS  Google Scholar 

  18. Gutsche, C.D., Maycock, J.R. & Chang, C.T. Tetrahedron 24, 859–876 (1968).

    Article  Google Scholar 

  19. Gutta, P. & Tantillo, D.J. J. Am. Chem. Soc. 128, 6172–6179 (2006).

    Article  CAS  Google Scholar 

  20. Song, L.J. et al. J. Am. Chem. Soc. 128, 14754–14755 (2006).

    Article  CAS  Google Scholar 

  21. Zhang, A. et al. Proc. Natl. Acad. Sci. USA 101, 9601–9606 (2004).

    Article  CAS  Google Scholar 

  22. Gunawardena, K., Rivera, S.B. & Epstein, W.W. Phytochemistry 59, 197–203 (2002).

    Article  CAS  Google Scholar 

  23. Heathcock, C.H., Finkelstein, B.L., Aoki, T. & Poulter, C.D. Science 229, 862–864 (1985).

    Article  CAS  Google Scholar 

  24. Staunton, J. & Weissman, K.J. Nat. Prod. Rep. 18, 380–416 (2001).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors acknowledge support from the Howard Hughes Medical Institute, the US National Institutes of Health and the US National Science Foundation.

Author information

Authors and Affiliations

  1. Michael B. Austin, Paul E. O'Maille and Joseph P. Noel are in the Howard Hughes Medical Institute, The Salk Institute for Biological Studies, Jack H. Skirball Center for Chemical Biology and Proteomics, 10010 North Torrey Pines Road, La Jolla, California 92037, USA. noel@salk.edu,

    Michael B Austin, Paul E O'Maille & Joseph P Noel

Authors
  1. Michael B Austin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Paul E O'Maille
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Joseph P Noel
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Austin, M., O'Maille, P. & Noel, J. Evolving biosynthetic tangos negotiate mechanistic landscapes. Nat Chem Biol 4, 217–222 (2008). https://doi.org/10.1038/nchembio0408-217

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio0408-217

  • Springer Nature America, Inc.

Search

Navigation