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 journalArticlepeer-review


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 languageEnglish
Article number5619
JournalNature Communications
Issue number1
Publication statusPublished - 12 Sept 2023

Bibliographical note

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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.


  • Cell Membrane
  • Fatty Acids, Nonesterified
  • Membranes
  • Polyphenols/pharmacology
  • Resveratrol


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