Evolutionary radiation of lanthipeptides in marine cyanobacteria
Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide...
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National Academy of Sciences (U.S.)
2018
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| Online Access: | http://hdl.handle.net/1721.1/114915 https://orcid.org/0000-0002-8566-5567 https://orcid.org/0000-0003-2795-2418 https://orcid.org/0000-0003-4564-3192 https://orcid.org/0000-0003-1480-2445 |
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| author | van der Donk, Wilfred A. Cubillos, Andres Fernando Becker, Jamie William Thompson, Jessica Weidemier Chisholm, Sallie (Penny) |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology van der Donk, Wilfred A. Cubillos, Andres Fernando Becker, Jamie William Thompson, Jessica Weidemier Chisholm, Sallie (Penny) |
| author_sort | van der Donk, Wilfred A. |
| collection | MIT |
| description | Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria use an unprecedented mechanism of substrate promiscuity for the production of numerous and diverse lanthipeptides using a single lanthionine synthetase. Through a cross-scale analysis of prochlorosin biosynthesis genes-from genomes to oceanic populations-we show that marine picocyanobacteria have the collective capacity to encode thousands of different cyclic peptides, few of which would display similar ring topologies. To understand how this extensive structural diversity arises, we used deep sequencing of wild populations to reveal genetic variation patterns in prochlorosin genes. We present evidence that structural variability among prochlorosins is the result of a diversifying selection process that favors large, rather than small, sequence changes in the precursor peptide genes. This mode of molecular evolution disregards any conservation of the ancestral structure and enables the emergence of extensively different cyclic peptides through short mutational paths based on indels. Contrary to its fast-evolving peptide substrates, the prochlorosin lanthionine synthetase evolves under a strong purifying selection, indicating that the diversification of prochlorosins is not constrained by commensurate changes in the biosynthetic enzyme. This evolutionary interplay between the prochlorosin peptide substrates and the lanthionine synthetase suggests that structure diversification, rather than structure refinement, is the driving force behind the creation of new prochlorosin structures and represents an intriguing mechanism by which natural product diversity arises. Keywords: lanthipeptides; prochlorosin; RiPPs; Prochlorococcus; Synechococcus |
| first_indexed | 2024-09-23T16:04:11Z |
| format | Article |
| id | mit-1721.1/114915 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:04:11Z |
| publishDate | 2018 |
| publisher | National Academy of Sciences (U.S.) |
| record_format | dspace |
| spelling | mit-1721.1/1149152022-10-02T06:08:58Z Evolutionary radiation of lanthipeptides in marine cyanobacteria van der Donk, Wilfred A. Cubillos, Andres Fernando Becker, Jamie William Thompson, Jessica Weidemier Chisholm, Sallie (Penny) Massachusetts Institute of Technology. Department of Biology Massachusetts Institute of Technology. Department of Civil and Environmental Engineering Cubillos, Andres Fernando Berta-Thompson, Jessica Weidemier Becker, Jamie William Chisholm, Sallie W Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria use an unprecedented mechanism of substrate promiscuity for the production of numerous and diverse lanthipeptides using a single lanthionine synthetase. Through a cross-scale analysis of prochlorosin biosynthesis genes-from genomes to oceanic populations-we show that marine picocyanobacteria have the collective capacity to encode thousands of different cyclic peptides, few of which would display similar ring topologies. To understand how this extensive structural diversity arises, we used deep sequencing of wild populations to reveal genetic variation patterns in prochlorosin genes. We present evidence that structural variability among prochlorosins is the result of a diversifying selection process that favors large, rather than small, sequence changes in the precursor peptide genes. This mode of molecular evolution disregards any conservation of the ancestral structure and enables the emergence of extensively different cyclic peptides through short mutational paths based on indels. Contrary to its fast-evolving peptide substrates, the prochlorosin lanthionine synthetase evolves under a strong purifying selection, indicating that the diversification of prochlorosins is not constrained by commensurate changes in the biosynthetic enzyme. This evolutionary interplay between the prochlorosin peptide substrates and the lanthionine synthetase suggests that structure diversification, rather than structure refinement, is the driving force behind the creation of new prochlorosin structures and represents an intriguing mechanism by which natural product diversity arises. Keywords: lanthipeptides; prochlorosin; RiPPs; Prochlorococcus; Synechococcus Gordon and Betty Moore Foundation (Grant GBMF495) 2018-04-24T13:42:28Z 2018-04-24T13:42:28Z 2017-06 2017-01 2018-04-20T13:19:08Z Article http://purl.org/eprint/type/ConferencePaper 0027-8424 1091-6490 http://hdl.handle.net/1721.1/114915 Cubillos-Ruiz, Andres et al. “Evolutionary Radiation of Lanthipeptides in Marine Cyanobacteria.” Proceedings of the National Academy of Sciences 114, 27 (June 2017): E5424–E5433 © 2017 The Authors https://orcid.org/0000-0002-8566-5567 https://orcid.org/0000-0003-2795-2418 https://orcid.org/0000-0003-4564-3192 https://orcid.org/0000-0003-1480-2445 http://dx.doi.org/10.1073/PNAS.1700990114 Proceedings of the National Academy of Sciences Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf National Academy of Sciences (U.S.) National Academy of Sciences |
| spellingShingle | van der Donk, Wilfred A. Cubillos, Andres Fernando Becker, Jamie William Thompson, Jessica Weidemier Chisholm, Sallie (Penny) Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title | Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title_full | Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title_fullStr | Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title_full_unstemmed | Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title_short | Evolutionary radiation of lanthipeptides in marine cyanobacteria |
| title_sort | evolutionary radiation of lanthipeptides in marine cyanobacteria |
| url | http://hdl.handle.net/1721.1/114915 https://orcid.org/0000-0002-8566-5567 https://orcid.org/0000-0003-2795-2418 https://orcid.org/0000-0003-4564-3192 https://orcid.org/0000-0003-1480-2445 |
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