Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery
- Autores
- Schottlender, Gustavo Ezequiel; Prieto, Juan Manuel; Clemente, Camila Mara; Schuster, Claudio David; Dumas, Victoria; Fernández Do Porto, Darío Augusto; Marti, Marcelo Adrian
- Año de publicación
- 2024
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Bacterial P450 cytochromes (BacCYPs) are versatile heme-containing proteins responsible for oxidation reactions on a wide range of substrates, contributing to the production of valuable natural products with limitless biotechnological potential. While the sequencing of microbial genomes has provided a wealth of BacCYP sequences, functional characterization lags behind, hindering our understanding of their roles. This study employs a comprehensive approach to predict BacCYP substrate specificity, bridging the gap between sequence and function. We employed an integrated approach combining sequence and functional data analysis, genomic context exploration, 3D structural modeling with molecular docking, and phylogenetic clustering. The research begins with an in-depth analysis of BacCYP sequence diversity and structural characteristics, revealing conserved motifs and recurrent residues in the active site. Phylogenetic analysis identifies distinct groups within the BacCYP family based on sequence similarity. However, our study reveals that sequence alone does not consistently predict substrate specificity, necessitating additional perspectives. The study delves into the genetic context of BacCYPs, utilizing neighboring gene information to infer potential substrates, a method proven very effective in many cases. Molecular docking is employed to assess BacCYP-substrate interactions, confirming potential substrates and providing insights into selectivity. Finally, a comprehensive strategy is proposed for predicting BacCYP substrates, involving all the evaluated approaches. The effectiveness of this strategy is demonstrated with two case studies, highlighting its potential for substrate discovery.
Fil: Schottlender, Gustavo Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Prieto, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Clemente, Camila Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Schuster, Claudio David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina
Fil: Dumas, Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina
Fil: Fernández Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina - Materia
- Proteins
- Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- https://creativecommons.org/licenses/by/2.5/ar/
- Repositorio
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/257441
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Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discoverySchottlender, Gustavo EzequielPrieto, Juan ManuelClemente, Camila MaraSchuster, Claudio DavidDumas, VictoriaFernández Do Porto, Darío AugustoMarti, Marcelo AdrianProteinshttps://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Bacterial P450 cytochromes (BacCYPs) are versatile heme-containing proteins responsible for oxidation reactions on a wide range of substrates, contributing to the production of valuable natural products with limitless biotechnological potential. While the sequencing of microbial genomes has provided a wealth of BacCYP sequences, functional characterization lags behind, hindering our understanding of their roles. This study employs a comprehensive approach to predict BacCYP substrate specificity, bridging the gap between sequence and function. We employed an integrated approach combining sequence and functional data analysis, genomic context exploration, 3D structural modeling with molecular docking, and phylogenetic clustering. The research begins with an in-depth analysis of BacCYP sequence diversity and structural characteristics, revealing conserved motifs and recurrent residues in the active site. Phylogenetic analysis identifies distinct groups within the BacCYP family based on sequence similarity. However, our study reveals that sequence alone does not consistently predict substrate specificity, necessitating additional perspectives. The study delves into the genetic context of BacCYPs, utilizing neighboring gene information to infer potential substrates, a method proven very effective in many cases. Molecular docking is employed to assess BacCYP-substrate interactions, confirming potential substrates and providing insights into selectivity. Finally, a comprehensive strategy is proposed for predicting BacCYP substrates, involving all the evaluated approaches. The effectiveness of this strategy is demonstrated with two case studies, highlighting its potential for substrate discovery.Fil: Schottlender, Gustavo Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Prieto, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Clemente, Camila Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Schuster, Claudio David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Dumas, Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; ArgentinaFil: Fernández Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFrontiers Media2024-06info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfapplication/pdfapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/257441Schottlender, Gustavo Ezequiel; Prieto, Juan Manuel; Clemente, Camila Mara; Schuster, Claudio David; Dumas, Victoria; et al.; Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery; Frontiers Media; Frontiers in Microbiology; 15; 6-2024; 1-141664-302XCONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1343029/fullinfo:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1343029info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T09:43:51Zoai:ri.conicet.gov.ar:11336/257441instacron:CONICETInstitucionalhttp://ri.conicet.gov.ar/Organismo científico-tecnológicoNo correspondehttp://ri.conicet.gov.ar/oai/requestdasensio@conicet.gov.ar; lcarlino@conicet.gov.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:34982025-09-29 09:43:51.665CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
title |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
spellingShingle |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery Schottlender, Gustavo Ezequiel Proteins |
title_short |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
title_full |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
title_fullStr |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
title_full_unstemmed |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
title_sort |
Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery |
dc.creator.none.fl_str_mv |
Schottlender, Gustavo Ezequiel Prieto, Juan Manuel Clemente, Camila Mara Schuster, Claudio David Dumas, Victoria Fernández Do Porto, Darío Augusto Marti, Marcelo Adrian |
author |
Schottlender, Gustavo Ezequiel |
author_facet |
Schottlender, Gustavo Ezequiel Prieto, Juan Manuel Clemente, Camila Mara Schuster, Claudio David Dumas, Victoria Fernández Do Porto, Darío Augusto Marti, Marcelo Adrian |
author_role |
author |
author2 |
Prieto, Juan Manuel Clemente, Camila Mara Schuster, Claudio David Dumas, Victoria Fernández Do Porto, Darío Augusto Marti, Marcelo Adrian |
author2_role |
author author author author author author |
dc.subject.none.fl_str_mv |
Proteins |
topic |
Proteins |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Bacterial P450 cytochromes (BacCYPs) are versatile heme-containing proteins responsible for oxidation reactions on a wide range of substrates, contributing to the production of valuable natural products with limitless biotechnological potential. While the sequencing of microbial genomes has provided a wealth of BacCYP sequences, functional characterization lags behind, hindering our understanding of their roles. This study employs a comprehensive approach to predict BacCYP substrate specificity, bridging the gap between sequence and function. We employed an integrated approach combining sequence and functional data analysis, genomic context exploration, 3D structural modeling with molecular docking, and phylogenetic clustering. The research begins with an in-depth analysis of BacCYP sequence diversity and structural characteristics, revealing conserved motifs and recurrent residues in the active site. Phylogenetic analysis identifies distinct groups within the BacCYP family based on sequence similarity. However, our study reveals that sequence alone does not consistently predict substrate specificity, necessitating additional perspectives. The study delves into the genetic context of BacCYPs, utilizing neighboring gene information to infer potential substrates, a method proven very effective in many cases. Molecular docking is employed to assess BacCYP-substrate interactions, confirming potential substrates and providing insights into selectivity. Finally, a comprehensive strategy is proposed for predicting BacCYP substrates, involving all the evaluated approaches. The effectiveness of this strategy is demonstrated with two case studies, highlighting its potential for substrate discovery. Fil: Schottlender, Gustavo Ezequiel. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Prieto, Juan Manuel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Clemente, Camila Mara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Schuster, Claudio David. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina Fil: Dumas, Victoria. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina Fil: Fernández Do Porto, Darío Augusto. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Cálculo; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina Fil: Marti, Marcelo Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentina |
description |
Bacterial P450 cytochromes (BacCYPs) are versatile heme-containing proteins responsible for oxidation reactions on a wide range of substrates, contributing to the production of valuable natural products with limitless biotechnological potential. While the sequencing of microbial genomes has provided a wealth of BacCYP sequences, functional characterization lags behind, hindering our understanding of their roles. This study employs a comprehensive approach to predict BacCYP substrate specificity, bridging the gap between sequence and function. We employed an integrated approach combining sequence and functional data analysis, genomic context exploration, 3D structural modeling with molecular docking, and phylogenetic clustering. The research begins with an in-depth analysis of BacCYP sequence diversity and structural characteristics, revealing conserved motifs and recurrent residues in the active site. Phylogenetic analysis identifies distinct groups within the BacCYP family based on sequence similarity. However, our study reveals that sequence alone does not consistently predict substrate specificity, necessitating additional perspectives. The study delves into the genetic context of BacCYPs, utilizing neighboring gene information to infer potential substrates, a method proven very effective in many cases. Molecular docking is employed to assess BacCYP-substrate interactions, confirming potential substrates and providing insights into selectivity. Finally, a comprehensive strategy is proposed for predicting BacCYP substrates, involving all the evaluated approaches. The effectiveness of this strategy is demonstrated with two case studies, highlighting its potential for substrate discovery. |
publishDate |
2024 |
dc.date.none.fl_str_mv |
2024-06 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://hdl.handle.net/11336/257441 Schottlender, Gustavo Ezequiel; Prieto, Juan Manuel; Clemente, Camila Mara; Schuster, Claudio David; Dumas, Victoria; et al.; Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery; Frontiers Media; Frontiers in Microbiology; 15; 6-2024; 1-14 1664-302X CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/257441 |
identifier_str_mv |
Schottlender, Gustavo Ezequiel; Prieto, Juan Manuel; Clemente, Camila Mara; Schuster, Claudio David; Dumas, Victoria; et al.; Bacterial cytochrome P450s: a bioinformatics odyssey of substrate discovery; Frontiers Media; Frontiers in Microbiology; 15; 6-2024; 1-14 1664-302X CONICET Digital CONICET |
dc.language.none.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
info:eu-repo/semantics/altIdentifier/url/https://www.frontiersin.org/articles/10.3389/fmicb.2024.1343029/full info:eu-repo/semantics/altIdentifier/doi/10.3389/fmicb.2024.1343029 |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
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openAccess |
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application/pdf application/pdf application/pdf application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Frontiers Media |
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Frontiers Media |
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Consejo Nacional de Investigaciones Científicas y Técnicas |
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CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicas |
repository.mail.fl_str_mv |
dasensio@conicet.gov.ar; lcarlino@conicet.gov.ar |
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13.070432 |