Membrane manipulation by free fatty acids improves microbial plant polyphenol synthesis
Nature Communications, vol. 14, pp. 5619
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.
Authors 13
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany
Institute of Biotechnology, RWTH Aachen University, Worringer Weg 3, 52074, Aachen, Germany
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Affiliation as printed
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands
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Affiliation as printed
College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, UK
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Affiliation as printed
Institute for Information Processing, IBI-1: Molecular and Cellular Physiology, Forschungszentrum Jülich, 52425, Jülich, Germany
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Affiliation as printed
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany
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Affiliation as printed
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany
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Affiliation as printed
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands
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Affiliation as printed
Remembrane Srl, via San Francesco 40, 40026, Imola, Italy
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Aston University · University of Manchester
Affiliation as printed
College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, UK
Manchester Institute of Biotechnology and Department of Chemistry, University of Manchester, Manchester, UK
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Affiliation as printed
College of Health and Life Sciences, Aston University, Birmingham, B4 7ET, UK
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Affiliation as printed
Remembrane Srl, via San Francesco 40, 40026, Imola, Italy
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Affiliation as printed
Groningen Biomolecular Sciences and Biotechnology Institute, University of Groningen, 9747 AG, Groningen, The Netherlands
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Forschungszentrum Jülich · RWTH Aachen University
Affiliation as printed
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany. j.marienhagen@fz-juelich.de
Institute of Biotechnology, RWTH Aachen University, Worringer Weg 3, 52074, Aachen, Germany. j.marienhagen@fz-juelich.de
Institute of Bio- and Geosciences, IBG-1: Biotechnology, Forschungszentrum Jülich, 52425, Jülich, Germany
Institute of Biotechnology, RWTH Aachen University, Worringer Weg 3, 52074, Aachen, Germany
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