Octanoylation of early intermediates of mycobacterial methylglucose lipopolysaccharides
Autor(a) principal: | |
---|---|
Data de Publicação: | 2015 |
Outros Autores: | , , , , , , , , , |
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. |
id |
RCAP_01521abb88e14cae7d4b4d82e55e6722 |
---|---|
oai_identifier_str |
oai:estudogeral.uc.pt:10316/109320 |
network_acronym_str |
RCAP |
network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
repository_id_str |
7160 |
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 instacron:RCAAP |
instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
instacron_str |
RCAAP |
institution |
RCAAP |
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 |
repository.mail.fl_str_mv |
|
_version_ |
1817551864404639744 |