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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References
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.
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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
