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Biosynthetic engineering of nonribosomal peptide synthetases.
Journal article

Biosynthetic engineering of nonribosomal peptide synthetases.

  • Kries H Laboratory of Organic Chemistry, ETH Zurich, CH-8093, Zurich, Switzerland.
  • 2016-07-29
Published in:
  • Journal of peptide science : an official publication of the European Peptide Society. - 2016
NRPS
click chemistry
directed evolution
domain swap
enzyme engineering
gramicidin S
Amino Acid Sequence
Anti-Bacterial Agents
Click Chemistry
Daptomycin
Directed Molecular Evolution
Drug Design
Gene Expression
Gramicidin
Mutation
Peptide Synthases
Peptides
Protein Domains
Protein Engineering
English From the evolutionary melting pot of natural product synthetase genes, microorganisms elicit antibiotics, communication tools, and iron scavengers. Chemical biologists manipulate these genes to recreate similarly diverse and potent biological activities not on evolutionary time scales but within months. Enzyme engineering has progressed considerably in recent years and offers new screening, modelling, and design tools for natural product designers. Here, recent advances in enzyme engineering and their application to nonribosomal peptide synthetases are reviewed. Among the nonribosomal peptides that have been subjected to biosynthetic engineering are the antibiotics daptomycin, calcium-dependent antibiotic, and gramicidin S. With these peptides, incorporation of unnatural building blocks and modulation of bioactivities via various structural modifications have been successfully demonstrated. Natural product engineering on the biosynthetic level is not a reliable method yet. However, progress in the understanding and manipulation of biosynthetic pathways may enable the routine production of optimized peptide drugs in the near future. Copyright © 2016 European Peptide Society and John Wiley & Sons, Ltd.
Language
  • English
Open access status
closed
Identifiers
Persistent URL
https://sonar.ch/global/documents/139919
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