Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications

Abstract Novel approaches in synthetic biology focus on the bottom-up modular assembly of natural, modified natural or artificial components into molecular systems with functionalities not found in nature. A possible application for such techniques is the bioremediation of natural water sources cont...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Mirko Stauffer, Zöhre Ucurum, Daniel Harder, Dimitrios Fotiadis
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/cede18987b644fab93c3442631ccfd2c
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:cede18987b644fab93c3442631ccfd2c
record_format	dspace
spelling	oai:doaj.org-article:cede18987b644fab93c3442631ccfd2c2021-12-02T16:35:11ZEngineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications10.1038/s41598-021-96298-42045-2322https://doaj.org/article/cede18987b644fab93c3442631ccfd2c2021-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-96298-4https://doaj.org/toc/2045-2322Abstract Novel approaches in synthetic biology focus on the bottom-up modular assembly of natural, modified natural or artificial components into molecular systems with functionalities not found in nature. A possible application for such techniques is the bioremediation of natural water sources contaminated with small organic molecules (e.g., drugs and pesticides). A simple molecular system to actively accumulate and degrade pollutants could be a bionanoreactor composed of a liposome or polymersome scaffold combined with energizing- (e.g., light-driven proton pump), transporting- (e.g., proton-driven transporter) and degrading modules (e.g., enzyme). This work focuses on the engineering of a transport module specific for β-lactam antibiotics. We previously solved the crystal structure of a bacterial peptide transporter, which allowed us to improve the affinity for certain β-lactam antibiotics using structure-based mutagenesis combined with a bacterial uptake assay. We were able to identify specific mutations, which enhanced the affinity of the transporter for antibiotics containing certain structural features. Screening of potential compounds allowed for the identification of a β-lactam antibiotic ligand with relatively high affinity. Transport of antibiotics was evaluated using a solid-supported membrane electrophysiology assay. In summary, we have engineered a proton-driven β-lactam antibiotic translocation module, contributing to the growing toolset for bionanotechnological applications.Mirko StaufferZöhre UcurumDaniel HarderDimitrios FotiadisNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-10 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Mirko Stauffer Zöhre Ucurum Daniel Harder Dimitrios Fotiadis Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
description	Abstract Novel approaches in synthetic biology focus on the bottom-up modular assembly of natural, modified natural or artificial components into molecular systems with functionalities not found in nature. A possible application for such techniques is the bioremediation of natural water sources contaminated with small organic molecules (e.g., drugs and pesticides). A simple molecular system to actively accumulate and degrade pollutants could be a bionanoreactor composed of a liposome or polymersome scaffold combined with energizing- (e.g., light-driven proton pump), transporting- (e.g., proton-driven transporter) and degrading modules (e.g., enzyme). This work focuses on the engineering of a transport module specific for β-lactam antibiotics. We previously solved the crystal structure of a bacterial peptide transporter, which allowed us to improve the affinity for certain β-lactam antibiotics using structure-based mutagenesis combined with a bacterial uptake assay. We were able to identify specific mutations, which enhanced the affinity of the transporter for antibiotics containing certain structural features. Screening of potential compounds allowed for the identification of a β-lactam antibiotic ligand with relatively high affinity. Transport of antibiotics was evaluated using a solid-supported membrane electrophysiology assay. In summary, we have engineered a proton-driven β-lactam antibiotic translocation module, contributing to the growing toolset for bionanotechnological applications.
format	article
author	Mirko Stauffer Zöhre Ucurum Daniel Harder Dimitrios Fotiadis
author_facet	Mirko Stauffer Zöhre Ucurum Daniel Harder Dimitrios Fotiadis
author_sort	Mirko Stauffer
title	Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
title_short	Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
title_full	Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
title_fullStr	Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
title_full_unstemmed	Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
title_sort	engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/cede18987b644fab93c3442631ccfd2c
work_keys_str_mv	AT mirkostauffer engineeringandfunctionalcharacterizationofaprotondrivenblactamantibiotictranslocationmoduleforbionanotechnologicalapplications AT zohreucurum engineeringandfunctionalcharacterizationofaprotondrivenblactamantibiotictranslocationmoduleforbionanotechnologicalapplications AT danielharder engineeringandfunctionalcharacterizationofaprotondrivenblactamantibiotictranslocationmoduleforbionanotechnologicalapplications AT dimitriosfotiadis engineeringandfunctionalcharacterizationofaprotondrivenblactamantibiotictranslocationmoduleforbionanotechnologicalapplications
_version_	1718383719593541632

Engineering and functional characterization of a proton-driven β-lactam antibiotic translocation module for bionanotechnological applications

Ejemplares similares