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Biosynthesis: Is it time to go retro?


Artificial biosynthetic pathways are typically assembled and optimized progressively, from earlier to later steps. This commentary highlights the potential of an alternate regressive method for biochemical pathway design and generation, inspired by the retro-evolution hypothesis and the concept of retrosynthesis. In addition to being a pathway design tool, 'bioretrosynthesis' has potential as a construction and optimization methodology.

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Figure 1: The recruitment and retro-evolution hypotheses, illustrated with the biosynthesis of pHPG (4), a component of vancomycin-class antibiotics.
Figure 2: Recuitment biosynthesis versus bioretrosynthesis.


  1. Zhang, M.Q. et al. J. Med. Chem. 51, 5494–5497 (2008).

    Article  CAS  Google Scholar 

  2. Wilkinson, B. & Micklefield, J. Nat. Chem. Biol. 3, 379–386 (2007).

    Article  CAS  Google Scholar 

  3. Zhou, H., Xie, X. & Tang, Y. Curr. Opin. Biotechnol. 19, 590–596 (2008).

    Article  CAS  Google Scholar 

  4. Ro, D.K. et al. Nature 440, 940–943 (2006).

    Article  CAS  Google Scholar 

  5. Li, W., Xie, D. & Frost, J.W. J. Am. Chem. Soc. 127, 2874–2882 (2005).

    Article  CAS  Google Scholar 

  6. Marner, W.D. II. Biotechnol. J. 4, 1406–1419 (2009).

    Article  CAS  Google Scholar 

  7. Jensen, R.A. Annu. Rev. Microbiol. 30, 409–425 (1976).

    Article  CAS  Google Scholar 

  8. Hubbard, B.K., Thomas, M.G. & Walsh, C.T. Chem. Biol. 7, 931–942 (2000).

    Article  CAS  Google Scholar 

  9. Carothers, J.M., Goler, J.A. & Keasling, J.D. Curr. Opin. Biotechnol. 20, 498–503 (2009).

    Article  CAS  Google Scholar 

  10. Metzenberg, R.L. Genetics 171, 1445–1448 (2005).

    PubMed  PubMed Central  Google Scholar 

  11. Horowitz, N.H. Proc. Natl. Acad. Sci. USA 31, 153–157 (1945).

    Article  CAS  Google Scholar 

  12. Johnson, A.P. et al. Science 322, 404 (2008).

    Article  CAS  Google Scholar 

  13. Corey, E.J. Angew. Chem. Int. Edn Engl. 30, 455–456 (1991).

    Article  Google Scholar 

  14. Cheng, X-M. & Corey, E. J. . The Logic of Chemical Synthesis (Wiley, New York, 1995).

    Google Scholar 

  15. Prather, K.L. & Martin, C.H. Curr. Opin. Biotechnol. 19, 468–474 (2008).

    Article  Google Scholar 

  16. Cho, A. et al. BMC Syst. Biol. 4, 35 (2010).

    Article  Google Scholar 

  17. Larock, R.C. Comprehensive Organic Transformations: A Guide to Functional Group Preparations 2nd edn. (Wiley-VCH, New York, 1999).

    Google Scholar 

  18. Moutselos, K. et al. BMC Bioinformatics 10, 324 (2009).

    Article  Google Scholar 

Download references


This work is supported by the Vanderbilt Institute of Chemical Biology and US National Institutes of Health RO1 GM077189.

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Correspondence to Brian O Bachmann.

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Bachmann, B. Biosynthesis: Is it time to go retro?. Nat Chem Biol 6, 390–393 (2010).

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