Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians
Abstract
A large family of cytotoxic cyclic peptides exemplified by the patellamides has been isolated from ascidians harboring the obligate cyanobacterial symbionts Prochloron spp.. Genome sequence analysis of these symbionts has revealed that Prochloron spp. synthesize patellamides by a ribosomal pathway. To understand how this pathway evolved to produce a suite of related metabolites, we analyzed 46 prochloron-containing ascidians from the tropical Pacific Ocean for the presence of patellamide biosynthetic genes and taxonomic markers. Here, we show that Prochloron spp. generate a diverse library of patellamides using small, hypervariable cassettes within a conserved genetic background. Each symbiont strain contains a single pathway, and mixtures of symbionts within ascidians lead to the accumulation of chemical libraries. We used this information to engineer the production of a new cyclic peptide in Escherichia coli, thereby demonstrating the power of comparative analysis of closely related symbiotic pathways to direct the genetic synthesis of new molecules.
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- Authors
- Donia, M. S., Hathaway, B. J., Sudek, S., Haygood, M. G., Rosovitz, M. J., Ravel, J., & Schmidt, E. W.
- Affiliations
- University of Utah (US)
- Scripps Institution of Oceanography (US)
- Oregon Health & Science University (US)
- J. Craig Venter Institute (US)
- Corresponding author
- Schmidt, Eric W
- Venue
- Nature Chemical Biology
- Published
- 2006-11-05
- Volume
- 2
- Issue
- 12
- Pages
- 729-735
- ISSN
- 1552-4450 (ISSN-L)
- OpenAlex
- W2006378794
- Cited by
- 261
- References
- 38
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 4 · 2023: 5 · 2022: 8 · 2021: 8 · 2020: 9 · 2019: 13 · 2018: 15 · 2017: 10 · 2016: 17 · 2015: 20 · 2014: 19 · 2013: 15 · 2012: 20
- FWCI
- 9.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Nature Chemical Biology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- University of California, San Diego
- National Institute of General Medical Sciences (R01GM071425)
- Topics
- Health Sciences › Medicine › Pharmacology › Microbial Natural Products and Biosynthesis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biotechnology › Marine Sponges and Natural Products
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chemical Synthesis and Analysis
- Keywords
- Prochloron, cyanobacterial symbionts, marine ascidian, ribosomal peptide synthesis, combinatorial peptide libraries, biosynthetic gene clusters
- MeSH terms
- Cyanobacteria, Amino Acid Sequence, Animals, Base Sequence, DNA, Bacterial, Molecular Sequence Data, Symbiosis, Urochordata, Peptide Library, Combinatorial Chemistry Techniques
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