Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity

ABSTRACT 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 in...

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Autores principales:	José A. Manso, Daniela Nunes-Costa, Sandra Macedo-Ribeiro, Nuno Empadinhas, Pedro José Barbosa Pereira
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2019
Materias:	Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/e96b6303fd2544bea14cfd9d4e76843d
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spelling	oai:doaj.org-article:e96b6303fd2544bea14cfd9d4e76843d2021-11-15T15:55:25ZMolecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity10.1128/mBio.00239-192150-7511https://doaj.org/article/e96b6303fd2544bea14cfd9d4e76843d2019-06-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.00239-19https://doaj.org/toc/2150-7511ABSTRACT 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.José A. MansoDaniela Nunes-CostaSandra Macedo-RibeiroNuno EmpadinhasPedro José Barbosa PereiraAmerican Society for MicrobiologyarticleStreptacidiphilus jiangxiensisStreptomycetaceaeX-ray crystallographyantibiotic productionsmall-angle X-ray scatteringMicrobiologyQR1-502ENmBio, Vol 10, Iss 3 (2019)
institution	DOAJ
collection	DOAJ
language	EN
topic	Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Microbiology QR1-502
spellingShingle	Streptacidiphilus jiangxiensis Streptomycetaceae X-ray crystallography antibiotic production small-angle X-ray scattering Microbiology QR1-502 José A. Manso Daniela Nunes-Costa Sandra Macedo-Ribeiro Nuno Empadinhas Pedro José Barbosa Pereira Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
description	ABSTRACT 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.
format	article
author	José A. Manso Daniela Nunes-Costa Sandra Macedo-Ribeiro Nuno Empadinhas Pedro José Barbosa Pereira
author_facet	José A. Manso Daniela Nunes-Costa Sandra Macedo-Ribeiro Nuno Empadinhas Pedro José Barbosa Pereira
author_sort	José A. Manso
title	Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
title_short	Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
title_full	Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
title_fullStr	Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
title_full_unstemmed	Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity
title_sort	molecular fingerprints for a novel enzyme family in <italic toggle="yes">actinobacteria</italic> with glucosamine kinase activity
publisher	American Society for Microbiology
publishDate	2019
url	https://doaj.org/article/e96b6303fd2544bea14cfd9d4e76843d
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Molecular Fingerprints for a Novel Enzyme Family in <italic toggle="yes">Actinobacteria</italic> with Glucosamine Kinase Activity

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