The DOI matches its Crossref record; 38 of the 40 references it cites were found in a registry or an index.
Production of cyclic peptides and proteins in vivo
Open accessAbstract
Combinatorial libraries of synthetic and natural products are an important source of molecular information for the interrogation of biological targets. Methods for the intracellular production of libraries of small, stable molecules would be a valuable addition to existing library technologies by combining the discovery potential inherent in small molecules with the large library sizes that can be realized by intracellular methods. We have explored the use of split inteins ( in ternal pro teins ) for the intracellular catalysis of peptide backbone cyclization as a method for generating proteins and small peptides that are stabilized against cellular catabolism. The DnaE split intein from Synechocystis sp. PCC6803 was used to cyclize the Escherichia coli enzyme dihydrofolate reductase and to produce the cyclic, eight-amino acid tyrosinase inhibitor pseudostellarin F in bacteria. Cyclic dihydrofolate reductase displayed improved in vitro thermostability, and pseudostellarin F production was readily apparent in vivo through its inhibition of melanin production catalyzed by recombinant Streptomyces antibioticus tyrosinase. The ability to generate and screen for backbone cyclic products in vivo is an important milestone toward the goal of generating intracellular cyclic peptide and protein libraries.
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Metadata
- Authors
- Scott, C. P., Abel-Santos, E., Wall, M., Wahnon, D. C., & Benkovic, S. J.
- Affiliations
- Pennsylvania State University (US)
- Department of Chemistry, Pennsylvania State University, University Park, PA 16802-6300
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 1999-11-23
- Volume
- 96
- Issue
- 24
- Pages
- 13638-13643
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC24117
- OpenAlex
- W2152458717
- Cited by
- 402
- References
- 40
- Citations by year
- 2026: 9 · 2025: 13 · 2024: 13 · 2023: 15 · 2022: 13 · 2021: 15 · 2020: 13 · 2019: 9 · 2018: 15 · 2017: 24 · 2016: 14 · 2015: 12 · 2014: 30 · 2013: 19 · 2012: 13
- FWCI
- 4.14
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- National Institutes of Health
- National Institute of General Medical Sciences (GM19891-01, F32GM019891)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Structural Characterization
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Bacterial Genetics and Biotechnology
- Keywords
- split intein, cyclic peptides, dihydrofolate reductase, tyrosinase inhibitors, melanogenesis inhibition, Streptomyces antibioticus, Synechocystis sp. PCC 6803, thermal stability
- MeSH terms
- Bacterial Proteins, Genetic Engineering, Peptides, Cyclic, Tetrahydrofolate Dehydrogenase, Monophenol Monooxygenase
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