Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia

Abstract In nature, microorganisms often reside in symbiotic co‐existence providing nutrition, stability, and protection for each partner by applying “division of labor.” This principle may also be used for the overproduction of targeted compounds in bioprocesses. It requires the engineering of a sy...

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Main Authors: Tobias Müller, Simon Schick, Jonathan Beck, Georg Sprenger, Ralf Takors
Format: Article
Language:English
Published: Wiley-VCH 2023-01-01
Series:Engineering in Life Sciences
Subjects:
Online Access:https://doi.org/10.1002/elsc.202100158
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author Tobias Müller
Simon Schick
Jonathan Beck
Georg Sprenger
Ralf Takors
author_facet Tobias Müller
Simon Schick
Jonathan Beck
Georg Sprenger
Ralf Takors
author_sort Tobias Müller
collection DOAJ
description Abstract In nature, microorganisms often reside in symbiotic co‐existence providing nutrition, stability, and protection for each partner by applying “division of labor.” This principle may also be used for the overproduction of targeted compounds in bioprocesses. It requires the engineering of a synthetic co‐culture with distributed tasks for each partner. Thereby, the competition on precursors, redox cofactors, and energy—which occurs in a single host—is prevented. Current applications often focus on unidirectional interactions, that is, the product of partner A is used for the completion of biosynthesis by partner B. Here, we present a synthetically engineered Escherichia coli co‐culture of two engineered mutant strains marked by the essential interaction of the partners which is achieved by implemented auxotrophies. The tryptophan auxotrophic strain E. coli ANT‐3, only requiring small amounts of the aromatic amino acid, provides the auxotrophic anthranilate for the tryptophan producer E. coli TRP‐3. The latter produces a surplus of tryptophan which is used to showcase the suitability of the co‐culture to access related products in future applications. Co‐culture characterization revealed that the microbial consortium is remarkably functionally stable for a broad range of inoculation ratios. The range of robust and functional interaction may even be extended by proper glucose feeding which was shown in a two‐compartment bioreactor setting with filtrate exchange. This system even enables the use of the co‐culture in a parallel two‐level temperature setting which opens the door to access temperature sensitive products via heterologous production in E. coli in a continuous manner.
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spelling doaj.art-556ace944693474193aae60df30690fd2023-01-05T02:40:22ZengWiley-VCHEngineering in Life Sciences1618-02401618-28632023-01-01231n/an/a10.1002/elsc.202100158Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortiaTobias Müller0Simon Schick1Jonathan Beck2Georg Sprenger3Ralf Takors4Institute of Biochemical Engineering University of Stuttgart Stuttgart GermanyInstitute of Microbiology University of Stuttgart Stuttgart GermanyInstitute of Biochemical Engineering University of Stuttgart Stuttgart GermanyInstitute of Microbiology University of Stuttgart Stuttgart GermanyInstitute of Biochemical Engineering University of Stuttgart Stuttgart GermanyAbstract In nature, microorganisms often reside in symbiotic co‐existence providing nutrition, stability, and protection for each partner by applying “division of labor.” This principle may also be used for the overproduction of targeted compounds in bioprocesses. It requires the engineering of a synthetic co‐culture with distributed tasks for each partner. Thereby, the competition on precursors, redox cofactors, and energy—which occurs in a single host—is prevented. Current applications often focus on unidirectional interactions, that is, the product of partner A is used for the completion of biosynthesis by partner B. Here, we present a synthetically engineered Escherichia coli co‐culture of two engineered mutant strains marked by the essential interaction of the partners which is achieved by implemented auxotrophies. The tryptophan auxotrophic strain E. coli ANT‐3, only requiring small amounts of the aromatic amino acid, provides the auxotrophic anthranilate for the tryptophan producer E. coli TRP‐3. The latter produces a surplus of tryptophan which is used to showcase the suitability of the co‐culture to access related products in future applications. Co‐culture characterization revealed that the microbial consortium is remarkably functionally stable for a broad range of inoculation ratios. The range of robust and functional interaction may even be extended by proper glucose feeding which was shown in a two‐compartment bioreactor setting with filtrate exchange. This system even enables the use of the co‐culture in a parallel two‐level temperature setting which opens the door to access temperature sensitive products via heterologous production in E. coli in a continuous manner.https://doi.org/10.1002/elsc.202100158metabolic engineeringmutual auxotrophic dependencyspatially linked bioreactorssynthetic co‐culturetryptophan
spellingShingle Tobias Müller
Simon Schick
Jonathan Beck
Georg Sprenger
Ralf Takors
Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
Engineering in Life Sciences
metabolic engineering
mutual auxotrophic dependency
spatially linked bioreactors
synthetic co‐culture
tryptophan
title Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
title_full Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
title_fullStr Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
title_full_unstemmed Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
title_short Synthetic mutualism in engineered E. coli mutant strains as functional basis for microbial production consortia
title_sort synthetic mutualism in engineered e coli mutant strains as functional basis for microbial production consortia
topic metabolic engineering
mutual auxotrophic dependency
spatially linked bioreactors
synthetic co‐culture
tryptophan
url https://doi.org/10.1002/elsc.202100158
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