Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians

Mohamed S. Donia, Brian J. Hathaway, Sebastian Sudek, Margo G. Haygood, M. J. Rosovitz, Jacques Ravel, Eric W. Schmidt

Research output: Contribution to journalArticle

204 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)729-735
Number of pages7
JournalNature Chemical Biology
Volume2
Issue number12
DOIs
StatePublished - Dec 2006
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Cell Biology

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    Donia, M. S., Hathaway, B. J., Sudek, S., Haygood, M. G., Rosovitz, M. J., Ravel, J., & Schmidt, E. W. (2006). Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians. Nature Chemical Biology, 2(12), 729-735. https://doi.org/10.1038/nchembio829