Skip to main content

Thank you for visiting nature.com. 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.

Biosynthesis

Reprogramming assembly lines

Nature Chemistry volume 10, pages 245–247 (2018)Cite this article

Subjects

Rational engineering of biosynthetic assembly lines for production of new compounds is an attractive prospect, yet it presents many challenges. Learning from biology, some of the rules for expanding the chemical diversity of non-ribosomal peptides have been uncovered in two recent studies.

Non-ribosomal peptide synthetases (NRPSs) are giant multi-domain protein complexes capable of producing an exquisite array of peptide structures, with diverse applications in medicine and agriculture (for example, vancomycin, daptomycin, penicillins and phosphinothricin). These enzymes conform to a modular architecture, where each module consists of individual catalytic domains required for amino-acid selection, activation and condensation to the next amino acid. Minimally, an NRPS module consists of an adenylation (A) domain for amino-acid selection and activation, a condensation (C) domain to catalyse peptide bond formation, and a thiolation (T) domain onto which the amino acids or intermediates are covalently tethered1.

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

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

Buy

All prices are NET prices.

Figure 1: Reprogramming NRPS pathways by domain engineering and XU swapping.

References

  1. Hur, G. H., Vickery, C. R. & Burkart, M. D. Nat. Prod. Rep. 29, 1074–1098 (2012).

    Article  CAS  Google Scholar 

  2. Winn, M., Fyans, J. K., Zhuo, Y. & Micklefield, J. Nat. Prod. Rep. 33, 317–347 (2016).

    Article  CAS  Google Scholar 

  3. Tanovic, A., Samel, S. A., Essen, L.-O. & Marahiel, M. A. Science 321, 659–663 (2008).

    Article  CAS  Google Scholar 

  4. Drake, E. J. et al. Nature 529, 235–238 (2016).

    Article  CAS  Google Scholar 

  5. Reimer, J. M., Aloise, M. N., Harrison, P. M. & Martin Schmeing, T. Nature 529, 239–242 (2016).

    Article  CAS  Google Scholar 

  6. Niquille, D. L. et al. Nat. Chem. 10, 282–287 (2018).

    Article  CAS  Google Scholar 

  7. Conti, E., Stachelhaus, T., Marahiel, M. A. & Brick, P. EMBO J. 16, 4174–4183 (1997).

    Article  CAS  Google Scholar 

  8. Stachelhaus, T., Mootz, H. D. & Marahiel, M. A. 6, 493–505 (1999).

  9. Challis, G. L., Ravel, J. & Townsend, C. A. Chem. Biol. 7, 211–224 (2000).

    Article  CAS  Google Scholar 

  10. Miyanaga, A., Cieślak, J., Shinohara, Y., Kudo, F. & Eguchi, T. J. Biol. Chem. 289, 31448–31457 (2014).

    Article  CAS  Google Scholar 

  11. Zhang, K. et al. Chem. Biol. 20, 92–101 (2013).

    Article  CAS  Google Scholar 

  12. Bozhüyük, K. A. J. et al. Nat. Chem. 10, 275–281 (2018).

    Article  Google Scholar 

  13. Zhang, L. et al. Angew. Chemie Int. Ed. 56, 1740–1745 (2017).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Warwick Integrative Synthetic Biology Centre, School of Life sciences, University of Warwick, Coventry, CV4 7AL, UK

    Binuraj R. K. Menon

  2. Department of Chemistry, University of Warwick, Coventry, CV4 7AL, UK

    Matthew Jenner

Authors
  1. Binuraj R. K. Menon
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Matthew Jenner
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Binuraj R. K. Menon or Matthew Jenner.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Menon, B., Jenner, M. Reprogramming assembly lines. Nature Chem 10, 245–247 (2018). https://doi.org/10.1038/nchem.2941

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchem.2941

This article is cited by

Search

Advanced search

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