Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity
Autor(a) principal: | |
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Data de Publicação: | 2019 |
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/10316/107151 https://doi.org/10.1128/mBio.00239-19 |
Resumo: | Actinobacteria have long been the main source of antibiotics, secondary metabolites with tightly controlled biosynthesis by environmental and physiological factors. Phosphorylation of exogenous glucosamine has been suggested as a mechanism for incorporation of this extracellular material into secondary metabolite biosynthesis, but experimental evidence of specific glucosamine kinases in Actinobacteria is lacking. Here, we present the molecular fingerprints for the identification of a unique family of actinobacterial glucosamine kinases. Structural and biochemical studies on a distinctive kinase from the soil bacterium Streptacidiphilus jiangxiensis unveiled its preference for glucosamine and provided structural evidence of a phosphoryl transfer to this substrate. Conservation of glucosamine-contacting residues across a large number of uncharacterized actinobacterial proteins unveiled a specific glucosamine binding sequence motif. This family of kinases and their genetic context may represent the missing link for the incorporation of environmental glucosamine into the antibiotic biosynthesis pathways in Actinobacteria and can be explored to enhance antibiotic production.IMPORTANCE The discovery of novel enzymes involved in antibiotic biosynthesis pathways is currently a topic of utmost importance. The high levels of antibiotic resistance detected worldwide threaten our ability to combat infections and other 20th-century medical achievements, namely, organ transplantation or cancer chemotherapy. We have identified and characterized a unique family of enzymes capable of phosphorylating glucosamine to glucosamine-6-phosphate, a crucial molecule directly involved in the activation of antibiotic production pathways in Actinobacteria, nature's main source of antimicrobials. The consensus sequence identified for these glucosamine kinases will help establish a molecular fingerprint to reveal yet-uncharacterized sequences in antibiotic producers, which should have an important impact in biotechnological and biomedical applications, including the enhancement and optimization of antibiotic production. |
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Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase ActivityStreptacidiphilus jiangxiensisStreptomycetaceaeX-ray crystallographyantibiotic productionsmall-angle X-ray scatteringActinobacteriaAnti-Bacterial AgentsDNA FingerprintingGlucosamineGlucose-6-PhosphatePhosphorylationPhosphotransferasesProtein BindingRNA, Ribosomal, 16SSoil MicrobiologyActinobacteria have long been the main source of antibiotics, secondary metabolites with tightly controlled biosynthesis by environmental and physiological factors. Phosphorylation of exogenous glucosamine has been suggested as a mechanism for incorporation of this extracellular material into secondary metabolite biosynthesis, but experimental evidence of specific glucosamine kinases in Actinobacteria is lacking. Here, we present the molecular fingerprints for the identification of a unique family of actinobacterial glucosamine kinases. Structural and biochemical studies on a distinctive kinase from the soil bacterium Streptacidiphilus jiangxiensis unveiled its preference for glucosamine and provided structural evidence of a phosphoryl transfer to this substrate. Conservation of glucosamine-contacting residues across a large number of uncharacterized actinobacterial proteins unveiled a specific glucosamine binding sequence motif. This family of kinases and their genetic context may represent the missing link for the incorporation of environmental glucosamine into the antibiotic biosynthesis pathways in Actinobacteria and can be explored to enhance antibiotic production.IMPORTANCE The discovery of novel enzymes involved in antibiotic biosynthesis pathways is currently a topic of utmost importance. The high levels of antibiotic resistance detected worldwide threaten our ability to combat infections and other 20th-century medical achievements, namely, organ transplantation or cancer chemotherapy. We have identified and characterized a unique family of enzymes capable of phosphorylating glucosamine to glucosamine-6-phosphate, a crucial molecule directly involved in the activation of antibiotic production pathways in Actinobacteria, nature's main source of antimicrobials. The consensus sequence identified for these glucosamine kinases will help establish a molecular fingerprint to reveal yet-uncharacterized sequences in antibiotic producers, which should have an important impact in biotechnological and biomedical applications, including the enhancement and optimization of antibiotic production.American Society for Microbiology2019-05-14info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://hdl.handle.net/10316/107151http://hdl.handle.net/10316/107151https://doi.org/10.1128/mBio.00239-19eng2161-21292150-7511Manso, José A.Nunes-Costa, DanielaMacedo-Ribeiro, SandraEmpadinhas, NunoPereira, Pedro José Barbosainfo: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:RCAAP2023-06-12T09:16:20Zoai:estudogeral.uc.pt:10316/107151Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T21:23:30.836196Repositório 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 |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
title |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
spellingShingle |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity Manso, José A. Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Actinobacteria Anti-Bacterial Agents DNA Fingerprinting Glucosamine Glucose-6-Phosphate Phosphorylation Phosphotransferases Protein Binding RNA, Ribosomal, 16S Soil Microbiology |
title_short |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
title_full |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
title_fullStr |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
title_full_unstemmed |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
title_sort |
Molecular Fingerprints for a Novel Enzyme Family in Actinobacteria with Glucosamine Kinase Activity |
author |
Manso, José A. |
author_facet |
Manso, José A. Nunes-Costa, Daniela Macedo-Ribeiro, Sandra Empadinhas, Nuno Pereira, Pedro José Barbosa |
author_role |
author |
author2 |
Nunes-Costa, Daniela Macedo-Ribeiro, Sandra Empadinhas, Nuno Pereira, Pedro José Barbosa |
author2_role |
author author author author |
dc.contributor.author.fl_str_mv |
Manso, José A. Nunes-Costa, Daniela Macedo-Ribeiro, Sandra Empadinhas, Nuno Pereira, Pedro José Barbosa |
dc.subject.por.fl_str_mv |
Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Actinobacteria Anti-Bacterial Agents DNA Fingerprinting Glucosamine Glucose-6-Phosphate Phosphorylation Phosphotransferases Protein Binding RNA, Ribosomal, 16S Soil Microbiology |
topic |
Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Actinobacteria Anti-Bacterial Agents DNA Fingerprinting Glucosamine Glucose-6-Phosphate Phosphorylation Phosphotransferases Protein Binding RNA, Ribosomal, 16S Soil Microbiology |
description |
Actinobacteria have long been the main source of antibiotics, secondary metabolites with tightly controlled biosynthesis by environmental and physiological factors. Phosphorylation of exogenous glucosamine has been suggested as a mechanism for incorporation of this extracellular material into secondary metabolite biosynthesis, but experimental evidence of specific glucosamine kinases in Actinobacteria is lacking. Here, we present the molecular fingerprints for the identification of a unique family of actinobacterial glucosamine kinases. Structural and biochemical studies on a distinctive kinase from the soil bacterium Streptacidiphilus jiangxiensis unveiled its preference for glucosamine and provided structural evidence of a phosphoryl transfer to this substrate. Conservation of glucosamine-contacting residues across a large number of uncharacterized actinobacterial proteins unveiled a specific glucosamine binding sequence motif. This family of kinases and their genetic context may represent the missing link for the incorporation of environmental glucosamine into the antibiotic biosynthesis pathways in Actinobacteria and can be explored to enhance antibiotic production.IMPORTANCE The discovery of novel enzymes involved in antibiotic biosynthesis pathways is currently a topic of utmost importance. The high levels of antibiotic resistance detected worldwide threaten our ability to combat infections and other 20th-century medical achievements, namely, organ transplantation or cancer chemotherapy. We have identified and characterized a unique family of enzymes capable of phosphorylating glucosamine to glucosamine-6-phosphate, a crucial molecule directly involved in the activation of antibiotic production pathways in Actinobacteria, nature's main source of antimicrobials. The consensus sequence identified for these glucosamine kinases will help establish a molecular fingerprint to reveal yet-uncharacterized sequences in antibiotic producers, which should have an important impact in biotechnological and biomedical applications, including the enhancement and optimization of antibiotic production. |
publishDate |
2019 |
dc.date.none.fl_str_mv |
2019-05-14 |
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/10316/107151 http://hdl.handle.net/10316/107151 https://doi.org/10.1128/mBio.00239-19 |
url |
http://hdl.handle.net/10316/107151 https://doi.org/10.1128/mBio.00239-19 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
2161-2129 2150-7511 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.publisher.none.fl_str_mv |
American Society for Microbiology |
publisher.none.fl_str_mv |
American Society for Microbiology |
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 |
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