Cargando…

Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis

BACKGROUND: Bacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs ar...

Descripción completa

Detalles Bibliográficos
Autores principales: Makarova, Kira S., Blackburne, Brittney, Wolf, Yuri I., Nikolskaya, Anastasia, Karamycheva, Svetlana, Espinoza, Marlene, Barry, Clifton E., Bewley, Carole A., Koonin, Eugene V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: BioMed Central 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939145/
https://www.ncbi.nlm.nih.gov/pubmed/35313954
http://dx.doi.org/10.1186/s13062-022-00320-2
_version_ 1784672684043403264
author Makarova, Kira S.
Blackburne, Brittney
Wolf, Yuri I.
Nikolskaya, Anastasia
Karamycheva, Svetlana
Espinoza, Marlene
Barry, Clifton E.
Bewley, Carole A.
Koonin, Eugene V.
author_facet Makarova, Kira S.
Blackburne, Brittney
Wolf, Yuri I.
Nikolskaya, Anastasia
Karamycheva, Svetlana
Espinoza, Marlene
Barry, Clifton E.
Bewley, Carole A.
Koonin, Eugene V.
author_sort Makarova, Kira S.
collection PubMed
description BACKGROUND: Bacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression. RESULTS: We compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution. CONCLUSIONS: We demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-022-00320-2.
format Online
Article
Text
id pubmed-8939145
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher BioMed Central
record_format MEDLINE/PubMed
spelling pubmed-89391452022-03-23 Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis Makarova, Kira S. Blackburne, Brittney Wolf, Yuri I. Nikolskaya, Anastasia Karamycheva, Svetlana Espinoza, Marlene Barry, Clifton E. Bewley, Carole A. Koonin, Eugene V. Biol Direct Research BACKGROUND: Bacteria and archaea produce an enormous diversity of modified peptides that are involved in various forms of inter-microbial conflicts or communication. A vast class of such peptides are Ribosomally synthesized, Postranslationally modified Peptides (RiPPs), and a major group of RiPPs are graspetides, so named after ATP-grasp ligases that catalyze the formation of lactam and lactone linkages in these peptides. The diversity of graspetides, the multiple proteins encoded in the respective Biosynthetic Gene Clusters (BGCs) and their evolution have not been studied in full detail. In this work, we attempt a comprehensive analysis of the graspetide-encoding BGCs and report a variety of novel graspetide groups as well as ancillary proteins implicated in graspetide biosynthesis and expression. RESULTS: We compiled a comprehensive, manually curated set of graspetides that includes 174 families including 115 new families with distinct patterns of amino acids implicated in macrocyclization and further modification, roughly tripling the known graspetide diversity. We derived signature motifs for the leader regions of graspetide precursors that could be used to facilitate graspetide prediction. Graspetide biosynthetic gene clusters and specific precursors were identified in bacterial divisions not previously known to encode RiPPs, in particular, the parasitic and symbiotic bacteria of the Candidate phyla radiation. We identified Bacteroides-specific biosynthetic gene clusters (BGC) that include remarkable diversity of graspetides encoded in the same loci which predicted to be modified by the same ATP-grasp ligase. We studied in details evolution of recently characterized chryseoviridin BGCs and showed that duplication and horizonal gene exchange both contribute to the diversification of the graspetides during evolution. CONCLUSIONS: We demonstrate previously unsuspected diversity of graspetide sequences, even those associated with closely related ATP-grasp enzymes. Several previously unnoticed families of proteins associated with graspetide biosynthetic gene clusters are identified. The results of this work substantially expand the known diversity of RiPPs and can be harnessed to further advance approaches for their identification. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1186/s13062-022-00320-2. BioMed Central 2022-03-21 /pmc/articles/PMC8939145/ /pubmed/35313954 http://dx.doi.org/10.1186/s13062-022-00320-2 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/ (https://creativecommons.org/publicdomain/zero/1.0/) ) applies to the data made available in this article, unless otherwise stated in a credit line to the data.
spellingShingle Research
Makarova, Kira S.
Blackburne, Brittney
Wolf, Yuri I.
Nikolskaya, Anastasia
Karamycheva, Svetlana
Espinoza, Marlene
Barry, Clifton E.
Bewley, Carole A.
Koonin, Eugene V.
Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title_full Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title_fullStr Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title_full_unstemmed Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title_short Phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
title_sort phylogenomic analysis of the diversity of graspetides and proteins involved in their biosynthesis
topic Research
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939145/
https://www.ncbi.nlm.nih.gov/pubmed/35313954
http://dx.doi.org/10.1186/s13062-022-00320-2
work_keys_str_mv AT makarovakiras phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT blackburnebrittney phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT wolfyurii phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT nikolskayaanastasia phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT karamychevasvetlana phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT espinozamarlene phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT barrycliftone phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT bewleycarolea phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis
AT koonineugenev phylogenomicanalysisofthediversityofgraspetidesandproteinsinvolvedintheirbiosynthesis