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The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity
Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097286/ https://www.ncbi.nlm.nih.gov/pubmed/33480992 http://dx.doi.org/10.1093/molbev/msab015 |
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author | Baunach, Martin Chowdhury, Somak Stallforth, Pierre Dittmann, Elke |
author_facet | Baunach, Martin Chowdhury, Somak Stallforth, Pierre Dittmann, Elke |
author_sort | Baunach, Martin |
collection | PubMed |
description | Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing and matching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the A(core) domains, yet domain interfaces and the flexible A(sub) domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches. |
format | Online Article Text |
id | pubmed-8097286 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-80972862021-05-10 The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity Baunach, Martin Chowdhury, Somak Stallforth, Pierre Dittmann, Elke Mol Biol Evol Discoveries Nonribosomal peptides (NRP) are crucial molecular mediators in microbial ecology and provide indispensable drugs. Nevertheless, the evolution of the flexible biosynthetic machineries that correlates with the stunning structural diversity of NRPs is poorly understood. Here, we show that recombination is a key driver in the evolution of bacterial NRP synthetase (NRPS) genes across distant bacterial phyla, which has guided structural diversification in a plethora of NRP families by extensive mixing and matching of biosynthesis genes. The systematic dissection of a large number of individual recombination events did not only unveil a striking plurality in the nature and origin of the exchange units but allowed the deduction of overarching principles that enable the efficient exchange of adenylation (A) domain substrates while keeping the functionality of the dynamic multienzyme complexes. In the majority of cases, recombination events have targeted variable portions of the A(core) domains, yet domain interfaces and the flexible A(sub) domain remained untapped. Our results strongly contradict the widespread assumption that adenylation and condensation (C) domains coevolve and significantly challenge the attributed role of C domains as stringent selectivity filter during NRP synthesis. Moreover, they teach valuable lessons on the choice of natural exchange units in the evolution of NRPS diversity, which may guide future engineering approaches. Oxford University Press 2021-01-22 /pmc/articles/PMC8097286/ /pubmed/33480992 http://dx.doi.org/10.1093/molbev/msab015 Text en © The Author(s) 2021. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. https://creativecommons.org/licenses/by/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) ), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Discoveries Baunach, Martin Chowdhury, Somak Stallforth, Pierre Dittmann, Elke The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title | The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title_full | The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title_fullStr | The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title_full_unstemmed | The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title_short | The Landscape of Recombination Events That Create Nonribosomal Peptide Diversity |
title_sort | landscape of recombination events that create nonribosomal peptide diversity |
topic | Discoveries |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8097286/ https://www.ncbi.nlm.nih.gov/pubmed/33480992 http://dx.doi.org/10.1093/molbev/msab015 |
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