Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides

Detalhes bibliográficos
Autor(a) principal: Maranha, Ana
Data de Publicação: 2015
Outros Autores: Moynihan, Patrick J., Miranda, Vanessa, Correia Lourenço, Eva, Nunes-Costa, Daniela, Fraga, Joana, José Barbosa Pereira, Pedro, Macedo-Ribeiro, Sandra, Ventura, M. Rita, Clarke, Anthony J., Empadinhas, Nuno
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
Texto Completo: http://hdl.handle.net/10316/109320
https://doi.org/10.1038/srep13610
Resumo: Mycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition to the partial esterification of glucose or methylglucose units with short-chain fatty acids, octanoate was invariably detected on the MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers octanoate to glucosylglycerate (GG) and diglucosylglycerate (DGG), the earliest intermediates in MGLP biosynthesis. Enzymatic studies, synthetic chemistry, NMR spectroscopy and mass spectrometry approaches suggest that, in contrast to the prevailing consensus, octanoate is not esterified to the primary hydroxyl group of glycerate but instead to the C6 OH of the second glucose in DGG. These observations raise important new questions about the MGLP reducing end architecture and about subsequent biosynthetic steps. Functional characterization of this unique octanoyltransferase, whose gene has been proposed to be essential for M. tuberculosis growth, adds new insights into a vital mycobacterial pathway, which may inspire new drug discovery strategies.
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spelling Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharidesBacterial ProteinsFatty AcidsGlycosylationGlycosyltransferasesKineticsLipopolysaccharidesMagnetic Resonance SpectroscopyMass SpectrometryMycobacteriumRecombinant ProteinsSubstrate SpecificityMycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition to the partial esterification of glucose or methylglucose units with short-chain fatty acids, octanoate was invariably detected on the MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers octanoate to glucosylglycerate (GG) and diglucosylglycerate (DGG), the earliest intermediates in MGLP biosynthesis. Enzymatic studies, synthetic chemistry, NMR spectroscopy and mass spectrometry approaches suggest that, in contrast to the prevailing consensus, octanoate is not esterified to the primary hydroxyl group of glycerate but instead to the C6 OH of the second glucose in DGG. These observations raise important new questions about the MGLP reducing end architecture and about subsequent biosynthetic steps. Functional characterization of this unique octanoyltransferase, whose gene has been proposed to be essential for M. tuberculosis growth, adds new insights into a vital mycobacterial pathway, which may inspire new drug discovery strategies.Springer Nature2015-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/109320http://hdl.handle.net/10316/109320https://doi.org/10.1038/srep13610eng2045-2322Maranha, AnaMoynihan, Patrick J.Miranda, VanessaCorreia Lourenço, EvaNunes-Costa, DanielaFraga, JoanaJosé Barbosa Pereira, PedroMacedo-Ribeiro, SandraVentura, M. RitaClarke, Anthony J.Empadinhas, Nunoinfo:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-10-10T10:43:34Zoai:estudogeral.uc.pt:10316/109320Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:25:32.038845Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse
dc.title.none.fl_str_mv Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
title Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
spellingShingle Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
Maranha, Ana
Bacterial Proteins
Fatty Acids
Glycosylation
Glycosyltransferases
Kinetics
Lipopolysaccharides
Magnetic Resonance Spectroscopy
Mass Spectrometry
Mycobacterium
Recombinant Proteins
Substrate Specificity
title_short Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
title_full Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
title_fullStr Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
title_full_unstemmed Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
title_sort Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
author Maranha, Ana
author_facet Maranha, Ana
Moynihan, Patrick J.
Miranda, Vanessa
Correia Lourenço, Eva
Nunes-Costa, Daniela
Fraga, Joana
José Barbosa Pereira, Pedro
Macedo-Ribeiro, Sandra
Ventura, M. Rita
Clarke, Anthony J.
Empadinhas, Nuno
author_role author
author2 Moynihan, Patrick J.
Miranda, Vanessa
Correia Lourenço, Eva
Nunes-Costa, Daniela
Fraga, Joana
José Barbosa Pereira, Pedro
Macedo-Ribeiro, Sandra
Ventura, M. Rita
Clarke, Anthony J.
Empadinhas, Nuno
author2_role author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Maranha, Ana
Moynihan, Patrick J.
Miranda, Vanessa
Correia Lourenço, Eva
Nunes-Costa, Daniela
Fraga, Joana
José Barbosa Pereira, Pedro
Macedo-Ribeiro, Sandra
Ventura, M. Rita
Clarke, Anthony J.
Empadinhas, Nuno
dc.subject.por.fl_str_mv Bacterial Proteins
Fatty Acids
Glycosylation
Glycosyltransferases
Kinetics
Lipopolysaccharides
Magnetic Resonance Spectroscopy
Mass Spectrometry
Mycobacterium
Recombinant Proteins
Substrate Specificity
topic Bacterial Proteins
Fatty Acids
Glycosylation
Glycosyltransferases
Kinetics
Lipopolysaccharides
Magnetic Resonance Spectroscopy
Mass Spectrometry
Mycobacterium
Recombinant Proteins
Substrate Specificity
description Mycobacteria synthesize unique intracellular methylglucose lipopolysaccharides (MGLP) proposed to modulate fatty acid metabolism. In addition to the partial esterification of glucose or methylglucose units with short-chain fatty acids, octanoate was invariably detected on the MGLP reducing end. We have identified a novel sugar octanoyltransferase (OctT) that efficiently transfers octanoate to glucosylglycerate (GG) and diglucosylglycerate (DGG), the earliest intermediates in MGLP biosynthesis. Enzymatic studies, synthetic chemistry, NMR spectroscopy and mass spectrometry approaches suggest that, in contrast to the prevailing consensus, octanoate is not esterified to the primary hydroxyl group of glycerate but instead to the C6 OH of the second glucose in DGG. These observations raise important new questions about the MGLP reducing end architecture and about subsequent biosynthetic steps. Functional characterization of this unique octanoyltransferase, whose gene has been proposed to be essential for M. tuberculosis growth, adds new insights into a vital mycobacterial pathway, which may inspire new drug discovery strategies.
publishDate 2015
dc.date.none.fl_str_mv 2015-09-01
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://hdl.handle.net/10316/109320
http://hdl.handle.net/10316/109320
https://doi.org/10.1038/srep13610
url http://hdl.handle.net/10316/109320
https://doi.org/10.1038/srep13610
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv 2045-2322
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv Springer Nature
publisher.none.fl_str_mv Springer Nature
dc.source.none.fl_str_mv reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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instname_str Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
instacron_str RCAAP
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reponame_str Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
collection Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
repository.name.fl_str_mv Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação
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