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Computational Modelling of Metabolic Burden and Substrate Toxicity in Escherichia coli Carrying a Synthetic Metabolic Pathway

M. Demko, L. Chrást, P. Dvořák, J. Damborský, D. Šafránek,

. 2019 ; 7 (11) : . [pub] 20191111

Jazyk angličtina Země Švýcarsko

Typ dokumentu časopisecké články

Perzistentní odkaz   https://www.medvik.cz/link/bmc19044053

Grantová podpora
CZ.02.1.01/0.0/0.0/1_026/0008451 Czech Ministry of Education
CZ.02.1.01/0.0/0.0/16_019/000086 Czech Ministry of Education
LM2015047 Czech Ministry of Education
LM2015055 Czech Ministry of Education
GA18-00178S Grant Agency of Czech Republic
720776 Horizon 2020 Framework Programme
722610 Seventh Framework Programme

In our previous work, we designed and implemented a synthetic metabolic pathway for 1,2,3-trichloropropane (TCP) biodegradation in Escherichia coli. Significant effects of metabolic burden and toxicity exacerbation were observed on single cell and population levels. Deeper understanding of mechanisms underlying these effects is extremely important for metabolic engineering of efficient microbial cell factories for biotechnological processes. In this paper, we present a novel mathematical model of the pathway. The model addresses for the first time the combined effects of toxicity exacerbation and metabolic burden in the context of bacterial population growth. The model is calibrated with respect to the real data obtained with our original synthetically modified E. coli strain. Using the model, we explore the dynamics of the population growth along with the outcome of the TCP biodegradation pathway considering the toxicity exacerbation and metabolic burden. On the methodological side, we introduce a unique computational workflow utilising algorithmic methods of computer science for the particular modelling problem.

Citace poskytuje Crossref.org

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