Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis

Apilaasha Tharmasothirajan; Josef Melcr; John Linney; Thomas Gensch; Karin Krumbach; Karla Marlen Ernst; Christopher Brasnett; Paola Poggi; Andrew R. Pitt; Alan D. Goddard; Alexandros Chatgilialoglu; Siewert J. Marrink; Jan Marienhagen

doi:10.1038/s41467-023-40947-x

Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis

Apilaasha Tharmasothirajan, Josef Melcr, John Linney, Thomas Gensch, Karin Krumbach, Karla Marlen Ernst, Christopher Brasnett, Paola Poggi, Andrew R. Pitt, Alan D. Goddard, Alexandros Chatgilialoglu, Siewert J. Marrink, Jan Marienhagen^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

Abstract

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.

Original language	English
Article number	5619
Journal	Nature Communications
Volume	14
Issue number	1
DOIs	https://doi.org/10.1038/s41467-023-40947-x
Publication status	Published - 12 Sept 2023

Bibliographical note

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/.

Funding: This work was funded by the German Federal Ministry of Education and Research (BMBF, Grant. No. 031B0621, J. Marienhagen) and BBSRC award BB/R02152X/1 (A.D.G.) as part of the project “MeMBrane - MEmbrane Modulation for BiopRocess enhANcEment”, which is embedded in the ERA CoBioTech action of the ERA-NET Cofund under the European Union’s Horizon 2020 research and innovation program.

Keywords

Cell Membrane
Fatty Acids, Nonesterified
Membranes
Polyphenols/pharmacology
Resveratrol

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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/.
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Tharmasothirajan, A., Melcr, J., Linney, J., Gensch, T., Krumbach, K., Ernst, K. M., Brasnett, C., Poggi, P., Pitt, A. R., Goddard, A. D., Chatgilialoglu, A., Marrink, S. J., & Marienhagen, J. (2023). Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis. Nature Communications, 14(1), Article 5619. https://doi.org/10.1038/s41467-023-40947-x

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Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis

Abstract

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Keywords

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