Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy

Kód výsledku v IS VaVaI

<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F60077344%3A_____%2F23%3A00583797" target="_blank" >RIV/60077344:_____/23:00583797 - isvavai.cz</a>

Výsledek na webu

<a href="https://doi.org/10.1007/s00285-023-01935-3" target="_blank" >https://doi.org/10.1007/s00285-023-01935-3</a>

DOI - Digital Object Identifier

<a href="http://dx.doi.org/10.1007/s00285-023-01935-3" target="_blank" >10.1007/s00285-023-01935-3</a>

Jazyk výsledku

angličtina

Název v původním jazyce

Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy

Popis výsledku v původním jazyce

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.

Název v anglickém jazyce

Optimal protein production by a synthetic microbial consortium: coexistence, distribution of labor, and syntrophy

Popis výsledku anglicky

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.

Druh

J_imp - Článek v periodiku v databázi Web of Science

CEP obor

—

OECD FORD obor

10618 - Ecology

Projekt

<a href="/cs/project/EF18_053%2F0016982" target="_blank" >EF18_053/0016982: Mezinárodní mobility výzkumných a administrativních pracovníků Biologického centra</a><br>

Návaznosti

I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace

Rok uplatnění

2023

Kód důvěrnosti údajů

S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů

Název periodika

Journal of Mathematical Biology

ISSN

0303-6812

e-ISSN

1432-1416

Svazek periodika

87

Číslo periodika v rámci svazku

1

Stát vydavatele periodika

DE - Spolková republika Německo

Počet stran výsledku

36

Strana od-do

23

Kód UT WoS článku

001021487000002

EID výsledku v databázi Scopus

2-s2.0-85164154826