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Biosynthetic Plasticity Enables Production of Fluorinated Aurachins
Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explor...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496329/ https://www.ncbi.nlm.nih.gov/pubmed/32216075 http://dx.doi.org/10.1002/cbic.202000166 |
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author | Sester, Angela Stüer‐Patowsky, Katrin Hiller, Wolf Kloss, Florian Lütz, Stephan Nett, Markus |
author_facet | Sester, Angela Stüer‐Patowsky, Katrin Hiller, Wolf Kloss, Florian Lütz, Stephan Nett, Markus |
author_sort | Sester, Angela |
collection | PubMed |
description | Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro‐ and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D. |
format | Online Article Text |
id | pubmed-7496329 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | John Wiley and Sons Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-74963292020-09-25 Biosynthetic Plasticity Enables Production of Fluorinated Aurachins Sester, Angela Stüer‐Patowsky, Katrin Hiller, Wolf Kloss, Florian Lütz, Stephan Nett, Markus Chembiochem Communications Enzyme promiscuity has important implications in the field of biocatalysis. In some cases, structural analogues of simple metabolic building blocks can be processed through entire pathways to give natural product derivatives that are not readily accessible by chemical means. In this study, we explored the plasticity of the aurachin biosynthesis pathway with regard to using fluoro‐ and chloroanthranilic acids, which are not abundant in the bacterial producers of these quinolone antibiotics. The incorporation rates of the tested precursor molecules disclosed a regiopreference for halogen substitution as well as steric limitations of enzymatic substrate tolerance. Three previously undescribed fluorinated aurachin derivatives were produced in preparative amounts by fermentation and structurally characterized. Furthermore, their antibacterial activities were evaluated in comparison to their natural congener aurachin D. John Wiley and Sons Inc. 2020-05-05 2020-08-17 /pmc/articles/PMC7496329/ /pubmed/32216075 http://dx.doi.org/10.1002/cbic.202000166 Text en © 2020 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Communications Sester, Angela Stüer‐Patowsky, Katrin Hiller, Wolf Kloss, Florian Lütz, Stephan Nett, Markus Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title | Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title_full | Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title_fullStr | Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title_full_unstemmed | Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title_short | Biosynthetic Plasticity Enables Production of Fluorinated Aurachins |
title_sort | biosynthetic plasticity enables production of fluorinated aurachins |
topic | Communications |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7496329/ https://www.ncbi.nlm.nih.gov/pubmed/32216075 http://dx.doi.org/10.1002/cbic.202000166 |
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