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Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis
Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integr...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497605/ https://www.ncbi.nlm.nih.gov/pubmed/37699874 http://dx.doi.org/10.1038/s41467-023-40947-x |
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author | Tharmasothirajan, Apilaasha Melcr, Josef Linney, John Gensch, Thomas Krumbach, Karin Ernst, Karla Marlen Brasnett, Christopher Poggi, Paola Pitt, Andrew R. Goddard, Alan D. Chatgilialoglu, Alexandros Marrink, Siewert J. Marienhagen, Jan |
author_facet | Tharmasothirajan, Apilaasha Melcr, Josef Linney, John Gensch, Thomas Krumbach, Karin Ernst, Karla Marlen Brasnett, Christopher Poggi, Paola Pitt, Andrew R. Goddard, Alan D. Chatgilialoglu, Alexandros Marrink, Siewert J. Marienhagen, Jan |
author_sort | Tharmasothirajan, Apilaasha |
collection | PubMed |
description | Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integrity and transport processes. To increase the production performance of engineered cell factories, strategies have to be developed to mitigate these detrimental effects. Here, we examine the accumulation of the stilbenoid resveratrol in the cell membrane and cell wall during its production using Corynebacterium glutamicum and uncover the membrane rigidifying effect of this stilbenoid experimentally and with molecular dynamics simulations. A screen of free fatty acid supplements identifies palmitelaidic acid and linoleic acid as suitable additives to attenuate resveratrol’s cytotoxic effects resulting in a three-fold higher product titer. This cost-effective approach to counteract membrane-damaging effects of product accumulation is transferable to the microbial production of other polyphenols and may represent an engineering target for other membrane-active bioproducts. |
format | Online Article Text |
id | pubmed-10497605 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-104976052023-09-14 Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis Tharmasothirajan, Apilaasha Melcr, Josef Linney, John Gensch, Thomas Krumbach, Karin Ernst, Karla Marlen Brasnett, Christopher Poggi, Paola Pitt, Andrew R. Goddard, Alan D. Chatgilialoglu, Alexandros Marrink, Siewert J. Marienhagen, Jan Nat Commun Article Microbial synthesis of nutraceutically and pharmaceutically interesting plant polyphenols represents a more environmentally friendly alternative to chemical synthesis or plant extraction. However, most polyphenols are cytotoxic for microorganisms as they are believed to negatively affect cell integrity and transport processes. To increase the production performance of engineered cell factories, strategies have to be developed to mitigate these detrimental effects. Here, we examine the accumulation of the stilbenoid resveratrol in the cell membrane and cell wall during its production using Corynebacterium glutamicum and uncover the membrane rigidifying effect of this stilbenoid experimentally and with molecular dynamics simulations. A screen of free fatty acid supplements identifies palmitelaidic acid and linoleic acid as suitable additives to attenuate resveratrol’s cytotoxic effects resulting in a three-fold higher product titer. This cost-effective approach to counteract membrane-damaging effects of product accumulation is transferable to the microbial production of other polyphenols and may represent an engineering target for other membrane-active bioproducts. Nature Publishing Group UK 2023-09-12 /pmc/articles/PMC10497605/ /pubmed/37699874 http://dx.doi.org/10.1038/s41467-023-40947-x Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Tharmasothirajan, Apilaasha Melcr, Josef Linney, John Gensch, Thomas Krumbach, Karin Ernst, Karla Marlen Brasnett, Christopher Poggi, Paola Pitt, Andrew R. Goddard, Alan D. Chatgilialoglu, Alexandros Marrink, Siewert J. Marienhagen, Jan Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title | Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title_full | Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title_fullStr | Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title_full_unstemmed | Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title_short | Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
title_sort | membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10497605/ https://www.ncbi.nlm.nih.gov/pubmed/37699874 http://dx.doi.org/10.1038/s41467-023-40947-x |
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