Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation

Autores
Tolmie, Carmien; Do Aido Machado, Rodolpho; Ferroni, Felix Martín; Smit, Martha Sophia; Opperman, Diederik Johannes
Año de publicación
2020
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that primarily convert ketones to esters, but can also catalyze heteroatom oxidation. Several structural studies have highlighted the importance of the ‘control loop’ in BVMOs, which adopts different conformations during catalysis. Central to the ‘control loop’ is a conserved tryptophan that has been implicated in NADP(H) binding. BVMOAFL210 from Aspergillus flavus, however, contains a threonine in the equivalent position. Here, we report the structure of BVMOAFL210 in complex with NADP+ in both the ‘open’ and ‘closed’ conformations. In neither conformation does Thr513 contact the NADP+. Although mutagenesis of Thr513 did not significantly alter the substrate scope, changes in peroxyflavin stability and reaction rates were observed. Mutation of this position also brought about changes in the regio-and enantioselectivity of the enzyme. Moreover, lower rates of overoxidation during sulfoxidation of thioanisole were also observed.
Fil: Tolmie, Carmien. University of the Free State; Sudáfrica
Fil: Do Aido Machado, Rodolpho. University of the Free State; Sudáfrica
Fil: Ferroni, Felix Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. University of the Free State; Sudáfrica
Fil: Smit, Martha Sophia. University of the Free State; Sudáfrica
Fil: Opperman, Diederik Johannes. University of the Free State; Sudáfrica
Materia
BAEYER-VILLIGER MONOOXYGENASE
ESTER
LACTONE
REGIOSELECTIVITY
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:11336/174649
Acceder
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network_name_str CONICET Digital (CONICET)
spelling Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidationTolmie, CarmienDo Aido Machado, RodolphoFerroni, Felix MartínSmit, Martha SophiaOpperman, Diederik JohannesBAEYER-VILLIGER MONOOXYGENASEESTERLACTONEREGIOSELECTIVITYhttps://purl.org/becyt/ford/1.4https://purl.org/becyt/ford/1Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that primarily convert ketones to esters, but can also catalyze heteroatom oxidation. Several structural studies have highlighted the importance of the ‘control loop’ in BVMOs, which adopts different conformations during catalysis. Central to the ‘control loop’ is a conserved tryptophan that has been implicated in NADP(H) binding. BVMOAFL210 from Aspergillus flavus, however, contains a threonine in the equivalent position. Here, we report the structure of BVMOAFL210 in complex with NADP+ in both the ‘open’ and ‘closed’ conformations. In neither conformation does Thr513 contact the NADP+. Although mutagenesis of Thr513 did not significantly alter the substrate scope, changes in peroxyflavin stability and reaction rates were observed. Mutation of this position also brought about changes in the regio-and enantioselectivity of the enzyme. Moreover, lower rates of overoxidation during sulfoxidation of thioanisole were also observed.Fil: Tolmie, Carmien. University of the Free State; SudáfricaFil: Do Aido Machado, Rodolpho. University of the Free State; SudáfricaFil: Ferroni, Felix Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. University of the Free State; SudáfricaFil: Smit, Martha Sophia. University of the Free State; SudáfricaFil: Opperman, Diederik Johannes. University of the Free State; SudáfricaMultidisciplinary Digital Publishing Institute2020-03info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionhttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfapplication/pdfhttp://hdl.handle.net/11336/174649Tolmie, Carmien; Do Aido Machado, Rodolpho; Ferroni, Felix Martín; Smit, Martha Sophia; Opperman, Diederik Johannes; Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation; Multidisciplinary Digital Publishing Institute; Catalysts; 10; 3; 3-2020; 1-132073-4344CONICET DigitalCONICETenginfo:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4344/10/3/339info:eu-repo/semantics/altIdentifier/doi/10.3390/catal10030339info:eu-repo/semantics/openAccesshttps://creativecommons.org/licenses/by/2.5/ar/reponame:CONICET Digital (CONICET)instname:Consejo Nacional de Investigaciones Científicas y Técnicas2025-09-29T10:43:19Zoai:ri.conicet.gov.ar:11336/174649instacron: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 10:43:19.544CONICET Digital (CONICET) - Consejo Nacional de Investigaciones Científicas y Técnicasfalse
dc.title.none.fl_str_mv Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
title Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
spellingShingle Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
Tolmie, Carmien
BAEYER-VILLIGER MONOOXYGENASE
ESTER
LACTONE
REGIOSELECTIVITY
title_short Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
title_full Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
title_fullStr Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
title_full_unstemmed Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
title_sort Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation
dc.creator.none.fl_str_mv Tolmie, Carmien
Do Aido Machado, Rodolpho
Ferroni, Felix Martín
Smit, Martha Sophia
Opperman, Diederik Johannes
author Tolmie, Carmien
author_facet Tolmie, Carmien
Do Aido Machado, Rodolpho
Ferroni, Felix Martín
Smit, Martha Sophia
Opperman, Diederik Johannes
author_role author
author2 Do Aido Machado, Rodolpho
Ferroni, Felix Martín
Smit, Martha Sophia
Opperman, Diederik Johannes
author2_role author
author
author
author
dc.subject.none.fl_str_mv BAEYER-VILLIGER MONOOXYGENASE
ESTER
LACTONE
REGIOSELECTIVITY
topic BAEYER-VILLIGER MONOOXYGENASE
ESTER
LACTONE
REGIOSELECTIVITY
purl_subject.fl_str_mv https://purl.org/becyt/ford/1.4
https://purl.org/becyt/ford/1
dc.description.none.fl_txt_mv Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that primarily convert ketones to esters, but can also catalyze heteroatom oxidation. Several structural studies have highlighted the importance of the ‘control loop’ in BVMOs, which adopts different conformations during catalysis. Central to the ‘control loop’ is a conserved tryptophan that has been implicated in NADP(H) binding. BVMOAFL210 from Aspergillus flavus, however, contains a threonine in the equivalent position. Here, we report the structure of BVMOAFL210 in complex with NADP+ in both the ‘open’ and ‘closed’ conformations. In neither conformation does Thr513 contact the NADP+. Although mutagenesis of Thr513 did not significantly alter the substrate scope, changes in peroxyflavin stability and reaction rates were observed. Mutation of this position also brought about changes in the regio-and enantioselectivity of the enzyme. Moreover, lower rates of overoxidation during sulfoxidation of thioanisole were also observed.
Fil: Tolmie, Carmien. University of the Free State; Sudáfrica
Fil: Do Aido Machado, Rodolpho. University of the Free State; Sudáfrica
Fil: Ferroni, Felix Martín. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - Santa Fe; Argentina. Universidad Nacional del Litoral. Facultad de Bioquímica y Ciencias Biológicas. Departamento de Física; Argentina. University of the Free State; Sudáfrica
Fil: Smit, Martha Sophia. University of the Free State; Sudáfrica
Fil: Opperman, Diederik Johannes. University of the Free State; Sudáfrica
description Baeyer-Villiger monooxygenases (BVMOs) are flavin-dependent enzymes that primarily convert ketones to esters, but can also catalyze heteroatom oxidation. Several structural studies have highlighted the importance of the ‘control loop’ in BVMOs, which adopts different conformations during catalysis. Central to the ‘control loop’ is a conserved tryptophan that has been implicated in NADP(H) binding. BVMOAFL210 from Aspergillus flavus, however, contains a threonine in the equivalent position. Here, we report the structure of BVMOAFL210 in complex with NADP+ in both the ‘open’ and ‘closed’ conformations. In neither conformation does Thr513 contact the NADP+. Although mutagenesis of Thr513 did not significantly alter the substrate scope, changes in peroxyflavin stability and reaction rates were observed. Mutation of this position also brought about changes in the regio-and enantioselectivity of the enzyme. Moreover, lower rates of overoxidation during sulfoxidation of thioanisole were also observed.
publishDate 2020
dc.date.none.fl_str_mv 2020-03
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/11336/174649
Tolmie, Carmien; Do Aido Machado, Rodolpho; Ferroni, Felix Martín; Smit, Martha Sophia; Opperman, Diederik Johannes; Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation; Multidisciplinary Digital Publishing Institute; Catalysts; 10; 3; 3-2020; 1-13
2073-4344
CONICET Digital
CONICET
url http://hdl.handle.net/11336/174649
identifier_str_mv Tolmie, Carmien; Do Aido Machado, Rodolpho; Ferroni, Felix Martín; Smit, Martha Sophia; Opperman, Diederik Johannes; Natural variation in the ‘control loop’ of BVMOAFL210 and its influence on regioselectivity and sulfoxidation; Multidisciplinary Digital Publishing Institute; Catalysts; 10; 3; 3-2020; 1-13
2073-4344
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.mdpi.com/2073-4344/10/3/339
info:eu-repo/semantics/altIdentifier/doi/10.3390/catal10030339
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 Multidisciplinary Digital Publishing Institute
publisher.none.fl_str_mv Multidisciplinary Digital Publishing Institute
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 13.069144

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