In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis
- Autores
- Nicoll, Callum R.; Alvigini, Laura; Gottinger, Andrea; Cecchini, Domiziana; Mannucci, Barbara; Corana, Federica; Mascotti, María Laura; Mattevi, Andrea
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Metabolons are protein assemblies that perform a series of reactions in a metabolic pathway. However, the general importance and aptitude of metabolons for enzyme catalysis remain poorly understood. In animals, biosynthesis of coenzyme Q is currently attributed to ten different proteins, with COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9 forming the iconic COQ metabolon. Yet several reaction steps conducted by the metabolon remain enigmatic. To elucidate the prerequisites for animal coenzyme Q biosynthesis, we sought to construct the entire metabolon in vitro. Here we show that this approach, rooted in ancestral sequence reconstruction, reveals the enzymes responsible for the uncharacterized steps and captures the biosynthetic pathway in vitro. We demonstrate that COQ8, a kinase, increases and streamlines coenzyme Q production. Our findings provide crucial insight into how biocatalytic efficiency is regulated and enhanced by these biosynthetic engines in the context of the cell.
Fil: Nicoll, Callum R.. Universita degli Studi di Pavia; Italia
Fil: Alvigini, Laura. Universita degli Studi di Pavia; Italia
Fil: Gottinger, Andrea. Universita degli Studi di Pavia; Italia
Fil: Cecchini, Domiziana. Universita degli Studi di Pavia; Italia
Fil: Mannucci, Barbara. Universita degli Studi di Pavia; Italia
Fil: Corana, Federica. Universita degli Studi di Pavia; Italia
Fil: Mascotti, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. University of Groningen; Países Bajos
Fil: Mattevi, Andrea. Universita degli Studi di Pavia; Italia - Materia
-
COQ BIOSYNTHESIS
METABOLON
RECONSTRUCTION - 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:11336/257659
Ver los metadatos del registro completo
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In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesisNicoll, Callum R.Alvigini, LauraGottinger, AndreaCecchini, DomizianaMannucci, BarbaraCorana, FedericaMascotti, María LauraMattevi, AndreaCOQ BIOSYNTHESISMETABOLONRECONSTRUCTIONhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1https://purl.org/becyt/ford/1.6https://purl.org/becyt/ford/1Metabolons are protein assemblies that perform a series of reactions in a metabolic pathway. However, the general importance and aptitude of metabolons for enzyme catalysis remain poorly understood. In animals, biosynthesis of coenzyme Q is currently attributed to ten different proteins, with COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9 forming the iconic COQ metabolon. Yet several reaction steps conducted by the metabolon remain enigmatic. To elucidate the prerequisites for animal coenzyme Q biosynthesis, we sought to construct the entire metabolon in vitro. Here we show that this approach, rooted in ancestral sequence reconstruction, reveals the enzymes responsible for the uncharacterized steps and captures the biosynthetic pathway in vitro. We demonstrate that COQ8, a kinase, increases and streamlines coenzyme Q production. Our findings provide crucial insight into how biocatalytic efficiency is regulated and enhanced by these biosynthetic engines in the context of the cell.Fil: Nicoll, Callum R.. Universita degli Studi di Pavia; ItaliaFil: Alvigini, Laura. Universita degli Studi di Pavia; ItaliaFil: Gottinger, Andrea. Universita degli Studi di Pavia; ItaliaFil: Cecchini, Domiziana. Universita degli Studi di Pavia; ItaliaFil: Mannucci, Barbara. Universita degli Studi di Pavia; ItaliaFil: Corana, Federica. Universita degli Studi di Pavia; ItaliaFil: Mascotti, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. University of Groningen; Países BajosFil: Mattevi, Andrea. Universita degli Studi di Pavia; ItaliaNature2023-11info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/257659Nicoll, Callum R.; Alvigini, Laura; Gottinger, Andrea; Cecchini, Domiziana; Mannucci, Barbara; et al.; In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis; Nature; Nature Catalysis; 7; 2; 11-2023; 148-1602520-1158CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.nature.com/articles/s41929-023-01087-zinfo:eu-repo/semantics/altIdentifier/doi/10.1038/s41929-023-01087-zinfo:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:00:07Zoai:ri.conicet.gov.ar:11336/257659instacron: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 10:00:08.257CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse |
dc.title.none.fl_str_mv |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
title |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
spellingShingle |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis Nicoll, Callum R. COQ BIOSYNTHESIS METABOLON RECONSTRUCTION |
title_short |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
title_full |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
title_fullStr |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
title_full_unstemmed |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
title_sort |
In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis |
dc.creator.none.fl_str_mv |
Nicoll, Callum R. Alvigini, Laura Gottinger, Andrea Cecchini, Domiziana Mannucci, Barbara Corana, Federica Mascotti, María Laura Mattevi, Andrea |
author |
Nicoll, Callum R. |
author_facet |
Nicoll, Callum R. Alvigini, Laura Gottinger, Andrea Cecchini, Domiziana Mannucci, Barbara Corana, Federica Mascotti, María Laura Mattevi, Andrea |
author_role |
author |
author2 |
Alvigini, Laura Gottinger, Andrea Cecchini, Domiziana Mannucci, Barbara Corana, Federica Mascotti, María Laura Mattevi, Andrea |
author2_role |
author author author author author author author |
dc.subject.none.fl_str_mv |
COQ BIOSYNTHESIS METABOLON RECONSTRUCTION |
topic |
COQ BIOSYNTHESIS METABOLON RECONSTRUCTION |
purl_subject.fl_str_mv |
https://purl.org/becyt/ford/1.4 https://purl.org/becyt/ford/1 https://purl.org/becyt/ford/1.6 https://purl.org/becyt/ford/1 |
dc.description.none.fl_txt_mv |
Metabolons are protein assemblies that perform a series of reactions in a metabolic pathway. However, the general importance and aptitude of metabolons for enzyme catalysis remain poorly understood. In animals, biosynthesis of coenzyme Q is currently attributed to ten different proteins, with COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9 forming the iconic COQ metabolon. Yet several reaction steps conducted by the metabolon remain enigmatic. To elucidate the prerequisites for animal coenzyme Q biosynthesis, we sought to construct the entire metabolon in vitro. Here we show that this approach, rooted in ancestral sequence reconstruction, reveals the enzymes responsible for the uncharacterized steps and captures the biosynthetic pathway in vitro. We demonstrate that COQ8, a kinase, increases and streamlines coenzyme Q production. Our findings provide crucial insight into how biocatalytic efficiency is regulated and enhanced by these biosynthetic engines in the context of the cell. Fil: Nicoll, Callum R.. Universita degli Studi di Pavia; Italia Fil: Alvigini, Laura. Universita degli Studi di Pavia; Italia Fil: Gottinger, Andrea. Universita degli Studi di Pavia; Italia Fil: Cecchini, Domiziana. Universita degli Studi di Pavia; Italia Fil: Mannucci, Barbara. Universita degli Studi di Pavia; Italia Fil: Corana, Federica. Universita degli Studi di Pavia; Italia Fil: Mascotti, María Laura. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - San Luis. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis. Universidad Nacional de San Luis. Facultad de Ciencias Físico Matemáticas y Naturales. Instituto Multidisciplinario de Investigaciones Biológicas de San Luis; Argentina. University of Groningen; Países Bajos Fil: Mattevi, Andrea. Universita degli Studi di Pavia; Italia |
description |
Metabolons are protein assemblies that perform a series of reactions in a metabolic pathway. However, the general importance and aptitude of metabolons for enzyme catalysis remain poorly understood. In animals, biosynthesis of coenzyme Q is currently attributed to ten different proteins, with COQ3, COQ4, COQ5, COQ6, COQ7 and COQ9 forming the iconic COQ metabolon. Yet several reaction steps conducted by the metabolon remain enigmatic. To elucidate the prerequisites for animal coenzyme Q biosynthesis, we sought to construct the entire metabolon in vitro. Here we show that this approach, rooted in ancestral sequence reconstruction, reveals the enzymes responsible for the uncharacterized steps and captures the biosynthetic pathway in vitro. We demonstrate that COQ8, a kinase, increases and streamlines coenzyme Q production. Our findings provide crucial insight into how biocatalytic efficiency is regulated and enhanced by these biosynthetic engines in the context of the cell. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023-11 |
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/11336/257659 Nicoll, Callum R.; Alvigini, Laura; Gottinger, Andrea; Cecchini, Domiziana; Mannucci, Barbara; et al.; In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis; Nature; Nature Catalysis; 7; 2; 11-2023; 148-160 2520-1158 CONICET Digital CONICET |
url |
http://hdl.handle.net/11336/257659 |
identifier_str_mv |
Nicoll, Callum R.; Alvigini, Laura; Gottinger, Andrea; Cecchini, Domiziana; Mannucci, Barbara; et al.; In vitro construction of the COQ metabolon unveils the molecular determinants of coenzyme Q biosynthesis; Nature; Nature Catalysis; 7; 2; 11-2023; 148-160 2520-1158 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.nature.com/articles/s41929-023-01087-z info:eu-repo/semantics/altIdentifier/doi/10.1038/s41929-023-01087-z |
dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess https://creativecommons.org/licenses/by/2.5/ar/ |
eu_rights_str_mv |
openAccess |
rights_invalid_str_mv |
https://creativecommons.org/licenses/by/2.5/ar/ |
dc.format.none.fl_str_mv |
application/pdf application/pdf |
dc.publisher.none.fl_str_mv |
Nature |
publisher.none.fl_str_mv |
Nature |
dc.source.none.fl_str_mv |
reponame:CONICET Digital (CONICET) instname:Consejo Nacional de Investigaciones Científicas y Técnicas |
reponame_str |
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CONICET Digital (CONICET) |
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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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1844613779206176768 |
score |
13.070432 |