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 and Jan Marienhagen ()
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Apilaasha Tharmasothirajan: Forschungszentrum Jülich
Josef Melcr: University of Groningen
John Linney: Aston University
Thomas Gensch: Forschungszentrum Jülich
Karin Krumbach: Forschungszentrum Jülich
Karla Marlen Ernst: Forschungszentrum Jülich
Christopher Brasnett: University of Groningen
Paola Poggi: Remembrane Srl
Andrew R. Pitt: Aston University
Alan D. Goddard: Aston University
Alexandros Chatgilialoglu: Remembrane Srl
Siewert J. Marrink: University of Groningen
Jan Marienhagen: Forschungszentrum Jülich

Nature Communications, 2023, vol. 14, issue 1, 1-14

Abstract: 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.

Date: 2023
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DOI: 10.1038/s41467-023-40947-x

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