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Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials

Coupling functional moieties to lantibiotics offers exciting opportunities to produce novel derivatives with desirable properties enabling new functions and applications. Here, five different synthetic hydrophobic polyproline peptides were conjugated to either nisin AB (the first two rings of nisin)...

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Autores principales: Deng, Jingjing, Viel, Jakob H., Kubyshkin, Vladimir, Budisa, Nediljko, Kuipers, Oscar P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715017/
https://www.ncbi.nlm.nih.gov/pubmed/33329435
http://dx.doi.org/10.3389/fmicb.2020.575334
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author Deng, Jingjing
Viel, Jakob H.
Kubyshkin, Vladimir
Budisa, Nediljko
Kuipers, Oscar P.
author_facet Deng, Jingjing
Viel, Jakob H.
Kubyshkin, Vladimir
Budisa, Nediljko
Kuipers, Oscar P.
author_sort Deng, Jingjing
collection PubMed
description Coupling functional moieties to lantibiotics offers exciting opportunities to produce novel derivatives with desirable properties enabling new functions and applications. Here, five different synthetic hydrophobic polyproline peptides were conjugated to either nisin AB (the first two rings of nisin) or nisin ABC (the first three rings of nisin) by using click chemistry. The antimicrobial activity of nisin ABC + O6K3 against Enterococcus faecium decreased 8-fold compared to full-length nisin, but its activity was 16-fold better than nisin ABC, suggesting that modifying nisin ABC is a promising strategy to generate semi-synthetic nisin hybrids. In addition, the resulting nisin hybrids are not prone to degradation at the C-terminus, which has been observed for nisin as it can be degraded by nisinase or other proteolytic enzymes. This methodology allows for getting more insight into the possibility of creating semi-synthetic nisin hybrids that maintain antimicrobial activity, in particular when synthetic and non-proteinaceous moieties are used. The success of this approach in creating viable nisin hybrids encourages further exploring the use of different modules, e.g., glycans, lipids, active peptide moieties, and other antimicrobial moieties.
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spelling pubmed-77150172020-12-15 Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials Deng, Jingjing Viel, Jakob H. Kubyshkin, Vladimir Budisa, Nediljko Kuipers, Oscar P. Front Microbiol Microbiology Coupling functional moieties to lantibiotics offers exciting opportunities to produce novel derivatives with desirable properties enabling new functions and applications. Here, five different synthetic hydrophobic polyproline peptides were conjugated to either nisin AB (the first two rings of nisin) or nisin ABC (the first three rings of nisin) by using click chemistry. The antimicrobial activity of nisin ABC + O6K3 against Enterococcus faecium decreased 8-fold compared to full-length nisin, but its activity was 16-fold better than nisin ABC, suggesting that modifying nisin ABC is a promising strategy to generate semi-synthetic nisin hybrids. In addition, the resulting nisin hybrids are not prone to degradation at the C-terminus, which has been observed for nisin as it can be degraded by nisinase or other proteolytic enzymes. This methodology allows for getting more insight into the possibility of creating semi-synthetic nisin hybrids that maintain antimicrobial activity, in particular when synthetic and non-proteinaceous moieties are used. The success of this approach in creating viable nisin hybrids encourages further exploring the use of different modules, e.g., glycans, lipids, active peptide moieties, and other antimicrobial moieties. Frontiers Media S.A. 2020-11-20 /pmc/articles/PMC7715017/ /pubmed/33329435 http://dx.doi.org/10.3389/fmicb.2020.575334 Text en Copyright © 2020 Deng, Viel, Kubyshkin, Budisa and Kuipers. http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Microbiology
Deng, Jingjing
Viel, Jakob H.
Kubyshkin, Vladimir
Budisa, Nediljko
Kuipers, Oscar P.
Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title_full Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title_fullStr Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title_full_unstemmed Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title_short Conjugation of Synthetic Polyproline Moietes to Lipid II Binding Fragments of Nisin Yields Active and Stable Antimicrobials
title_sort conjugation of synthetic polyproline moietes to lipid ii binding fragments of nisin yields active and stable antimicrobials
topic Microbiology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7715017/
https://www.ncbi.nlm.nih.gov/pubmed/33329435
http://dx.doi.org/10.3389/fmicb.2020.575334
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