Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis
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Published:2023-09-12
Issue:1
Volume:14
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Tharmasothirajan ApilaashaORCID, Melcr Josef, Linney John, Gensch ThomasORCID, Krumbach Karin, Ernst Karla Marlen, Brasnett ChristopherORCID, Poggi Paola, Pitt Andrew R., Goddard Alan D., Chatgilialoglu Alexandros, Marrink Siewert J.ORCID, Marienhagen JanORCID
Abstract
AbstractMicrobial 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.
Funder
Bundesministerium für Bildung und Forschung RCUK | Biotechnology and Biological Sciences Research Council
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry,Multidisciplinary
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