The DOI matches its Crossref record; 24 of the 24 references it cites were found in a registry or an index.
Combinatorial biosynthesis of novel antibiotics related to daptomycin
Open accessAbstract
Daptomycin, a cyclic lipopeptide produced by Streptomyces roseosporus , is the active ingredient of Cubicin (daptomycin-for-injection), a first-in-class antibiotic approved for treatment of skin and skin-structure infections caused by Gram-positive pathogens and bacteremia and endocarditis caused by Staphylococcus aureus , including methicillin-resistant strains. Genetic engineering of the nonribosomal peptide synthetase (NRPS) in the daptomycin biosynthetic pathway was exploited for the biosynthesis of novel active antibiotics. λ-Red-mediated recombination was used to exchange single or multiple modules in the DptBC subunit of the NRPS to modify the daptomycin cyclic peptide core. We combined module exchanges, NRPS subunit exchanges, inactivation of the tailoring enzyme glutamic acid 3-methyltransferase, and natural variations of the lipid tail to generate a library of novel lipopeptides, some of which were as active as daptomycin against Gram-positive bacteria. One compound was more potent against an Escherichia coli imp mutant that has increased outer membrane permeability. This study established a robust combinatorial biosynthesis platform to produce novel peptide antibiotics in sufficient quantities for antimicrobial screening and drug development.
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Cites
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Cited by
Ribosomal peptide natural products: bridging the ribosomal and nonribosomal worlds
McIntosh, J. A., Donia, M. S., & Schmidt, E. W. (2009) · Natural Product Reports · doi:10.1039/b714132g · Cited by 269
Recent advances in engineering nonribosomal peptide assembly lines
Winn, M., Fyans, J. K., Zhuo, Y., & Micklefield, J. (2016) · Natural Product Reports · doi:10.1039/c5np00099h · Cited by 266
Bioactive Peptides from Microalgae and Cyanobacteria and Their Possible Mechanisms of Action
Chitthan, S. V., Rasheed, A. S., Muniyandi, M., Dhanasekaran, D., & Thajuddin, N. (2025) · International Journal of Peptide Research and Therapeutics · doi:10.1007/s10989-025-10746-7 · Cited by 12
Metadata
- Authors
- Nguyen, K. T., Ritz, D., Gu, J.-Q., Alexander, D., Chu, M., Miao, V., Brian, P., & Baltz, R. H.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2006-11-14
- Volume
- 103
- Issue
- 46
- Pages
- 17462-17467
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2068815648
- Cited by
- 287
- References
- 24
- FWCI
- 7.92
- Type
- journal article
- Language
- en
- Open access
- green
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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