Letter abstract
Nature Chemical Biology 2, 729 - 735 (2006)
Published online: 5 November 2006 | doi:10.1038/nchembio829
Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians
Mohamed S Donia1,5, Brian J Hathaway1,5, Sebastian Sudek2, Margo G Haygood3, M J Rosovitz4, Jacques Ravel4 & Eric W Schmidt1
A large family of cytotoxic cyclic peptides exemplified by the patellamides has been isolated from ascidians harboring the obligate cyanobacterial symbionts Prochloron spp.1, 2, 3, 4, 5. Genome sequence analysis of these symbionts has revealed that Prochloron spp. synthesize patellamides by a ribosomal pathway6. 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.
- Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, USA.
- Scripps Institution of Oceanography, University of California San Diego, La Jolla, California 92037, USA.
- Department of Environmental and Biomolecular Systems, OGI School of Science & Engineering, Oregon Health & Science University, Beaverton, Oregon 97006, USA.
- The Institute for Genomic Research, Rockville, Maryland 20850, USA.
- These authors contributed equally to this work.
Correspondence to: Eric W Schmidt1 e-mail: ews1@utah.edu
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