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
CONICET Digital (CONICET)
Institución
Consejo Nacional de Investigaciones Científicas y Técnicas
OAI Identificador
oai:ri.conicet.gov.ar:11336/257659
Acceder
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network_acronym_str CONICETDig
repository_id_str 3498
network_name_str CONICET Digital (CONICET)
spelling 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 Técnicas2025-10-22T11:29:37Zoai: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:34982025-10-22 11:29:37.712CONICET 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 CONICET Digital (CONICET)
collection CONICET Digital (CONICET)
instname_str Consejo Nacional de Investigaciones Científicas y Técnicas
repository.name.fl_str_mv 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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score 12.982451

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