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
- Institución
- Consejo Nacional de Investigaciones Científicas y Técnicas
- OAI Identificador
- oai:ri.conicet.gov.ar:11336/174649
Ver los metadatos del registro completo
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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 Técnicas2025-09-03T10:10:35Zoai: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:34982025-09-03 10:10:35.899CONICET 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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1842270126020231168 |
score |
13.13397 |