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

doi:10.1038/nchembio829

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

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233 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 language	English (US)
Pages (from-to)	729-735
Number of pages	7
Journal	Nature Chemical Biology
Volume	2
Issue number	12
DOIs	https://doi.org/10.1038/nchembio829
State	Published - Dec 2006

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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title = "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.",

author = "Donia, {Mohamed S.} and Hathaway, {Brian J.} and Sebastian Sudek and Haygood, {Margo G.} and Rosovitz, {M. J.} and Jacques Ravel and Schmidt, {Eric W.}",

note = "Funding Information: This work was supported by grants from the US National Science Foundation (EF-0412226) and the US National Institutes of Health (R01 GM071425-01A1), and by a Willard L. Eccles Fellowship to B.J.H. We thank D.J. Faulkner (University of California San Diego), C. Ireland (University of Utah), L. Matainaho (University of Papua New Guinea) and the governments of the Republic of Palau and Papua New Guinea for the opportunities to collect the samples used in these studies. We also thank K. Rai and D. Jones (University of Utah) and L. Jiang (TIGR) for their help in the quantitative PCR experiments. T. Bugni (University of Utah) helped with mass measurements, and J. Sims (University of Utah) aided with sample processing.",

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Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians

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