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

Research output: Contribution to journal › Article › peer-review

236 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
Externally published	Yes

All Science Journal Classification (ASJC) codes

Molecular Biology
Cell Biology

Access to Document

10.1038/nchembio829

Cite this

@article{9f3aa9c7ef7f414396b74e4ffc76294a,

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.",

year = "2006",

month = dec,

doi = "10.1038/nchembio829",

language = "English (US)",

volume = "2",

pages = "729--735",

journal = "Nature Chemical Biology",

issn = "1552-4450",

publisher = "Nature Research",

number = "12",

}

TY - JOUR

T1 - Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians

AU - Donia, Mohamed S.

AU - Hathaway, Brian J.

AU - Sudek, Sebastian

AU - Haygood, Margo G.

AU - Rosovitz, M. J.

AU - Ravel, Jacques

AU - Schmidt, Eric W.

N1 - 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.

PY - 2006/12

Y1 - 2006/12

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=33751096434&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33751096434&partnerID=8YFLogxK

U2 - 10.1038/nchembio829

DO - 10.1038/nchembio829

M3 - Article

C2 - 17086177

AN - SCOPUS:33751096434

SN - 1552-4450

VL - 2

SP - 729

EP - 735

JO - Nature Chemical Biology

JF - Nature Chemical Biology

IS - 12

ER -

Natural combinatorial peptide libraries in cyanobacterial symbionts of marine ascidians

Abstract

All Science Journal Classification (ASJC) codes

Access to Document

Other files and links

Fingerprint

Cite this