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Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy
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SYSNO ASEP 0583797 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy Author(s) Martínez, Carlos (BC-A) RID, ORCID
Cinquemani, E. (FR)
de Jong, H. (FR)
Gouze, J. (FR)Number of authors 4 Article number 23 Source Title Journal of Mathematical Biology - ISSN 0303-6812
Roč. 87, č. 1 (2023)Number of pages 36 s. Language eng - English Country DE - Germany Keywords division-of-labor ; Microbial consortia ; Pareto optimality ; Dynamical systems ; Production of recombinant proteins Subject RIV EH - Ecology, Behaviour OECD category Ecology R&D Projects EF18_053/0016982 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Open access Institutional support BC-A - RVO:60077344 UT WOS 001021487000002 EID SCOPUS 85164154826 DOI 10.1007/s00285-023-01935-3 Annotation The bacterium E. coli is widely used to produce recombinant proteins such as growth hormone and insulin. One inconvenience with E. coli cultures is the secretion of acetate through overflow metabolism. Acetate inhibits cell growth and represents a carbon diversion, which results in several negative effects on protein production. One way to overcome this problem is the use of a synthetic consortium of two different E. coli strains, one producing recombinant proteins and one reducing the acetate concentration. In this paper, we study a mathematical model of such a synthetic community in a chemostat where both strains are allowed to produce recombinant proteins. We give necessary and sufficient conditions for the existence of a coexistence equilibrium and show that it is unique. Based on this equilibrium, we define a multi-objective optimization problem for the maximization of two important bioprocess performance metrics, process yield and productivity. Solving numerically this problem, we find the best available trade-offs between the metrics. Under optimal operation of the mixed community, both strains must produce the protein of interest, and not only one (distribution instead of division of labor). Moreover, in this regime acetate secretion by one strain is necessary for the survival of the other (syntrophy). The results thus illustrate how complex multi-level dynamics shape the optimal production of recombinant proteins by synthetic microbial consortia. Workplace Biology Centre (since 2006) Contact Dana Hypšová, eje@eje.cz, Tel.: 387 775 214 Year of Publishing 2024 Electronic address https://doi.org/10.1007/s00285-023-01935-3
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