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High-throughput engineering of biosynthetic assembly lines

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Nonribosomal peptide synthetases produce diverse natural products, including many valuable therapeutics. Although the condensation domains that catalyze peptide bond formation in these multifunctional enzymes have been difficult to engineer, a yeast display system that was developed to screen millions of variants now enables efficient reprogramming of synthetase substrate specificity.

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Fig. 1: NRPS-catalyzed peptide elongation on the surface of yeast.

References

  1. Süssmuth, R. D. & Mainz, A. Nonribosomal peptide synthesis—principles and prospects. Angew. Chem. Int. Ed. 56, 3770–3821 (2017). A review article that provides a general overview of NRPS chemistry.

    Article  Google Scholar 

  2. Bloudoff, K. & Schmeing, T. M. Structural and functional aspects of the nonribosomal peptide synthetase condensation domain superfamily: Discovery, dissection and diversity. Biochim. Biophys. Acta 1865, 1587–1604 (2017). This review article summarizes what is known about NRPS condensation domains.

    Article  CAS  Google Scholar 

  3. Zhang, K. et al. Engineering the substrate specificity of the DhbE adenylation domain by yeast cell surface display. Chem. Biol. 20, 92–101 (2013). This paper reports the display of an NRPS adenylation domain on yeast.

    Article  CAS  PubMed  Google Scholar 

  4. Niquille, D. L. et al. Nonribosomal biosynthesis of backbone-modified peptides. Nat. Chem. 10, 282–287 (2018). This paper describes a high-throughput catalytic assay for tailoring the substrate specificity of NRPS adenylation domains.

    Article  CAS  PubMed  Google Scholar 

  5. Kolb, H. C., Finn, M. G. & Sharpless, K. B. Click chemistry: diverse chemical function from a few good reactions. Angew. Chem. Int. Ed. 40, 2004–2021 (2001). This review article outlines the principles of click chemistry.

    Article  CAS  Google Scholar 

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This is a summary of: Folger, I. B. et al. High-throughput reprogramming of an NRPS condensation domain. Nat. Chem. Biol. https://doi.org/10.1038/s41589-023-01532-x (2024).

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High-throughput engineering of biosynthetic assembly lines. Nat Chem Biol (2024). https://doi.org/10.1038/s41589-024-01564-x

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  • DOI: https://doi.org/10.1038/s41589-024-01564-x

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