Metabolic flux responses to deletion of 20 core enzymes reveal flexibility and limits of E. coli metabolism.
Metab Eng
; 55: 249-257, 2019 09.
Article
en En
| MEDLINE
| ID: mdl-31390539
ABSTRACT
Despite remarkable progress in mapping biochemistry and gene-protein-reaction relationships, quantitative systems-level understanding of microbial metabolism remains a persistent challenge. Here, 13C-metabolic flux analysis was applied to interrogate metabolic responses to 20 genetic perturbations in all viable Escherichia coli single gene knockouts in upper central metabolic pathways. Strains with severe growth defects displayed highly altered intracellular flux patterns and were the most difficult to predict using current constraint-based modeling approaches. In the ΔpfkA strain, an unexpected glucose-secretion phenotype was identified. The broad range of flux rewiring responses that were quantified suggest that some compensating pathways are more flexible than others, resulting in a more robust physiology. The fact that only 2 out of 20 strains displayed an increased net pathway-flux capacity points to a fundamental rate limitation of E. coli core metabolism. In cataloguing the various cellular responses, our results provide a critical resource for kinetic model development and efforts focused on genotype-to-phenotype predictions.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas de Escherichia coli
/
Escherichia coli
/
Técnicas de Inactivación de Genes
/
Análisis de Flujos Metabólicos
/
Glucosa
/
Modelos Biológicos
Tipo de estudio:
Prognostic_studies
Idioma:
En
Revista:
Metab Eng
Asunto de la revista:
ENGENHARIA BIOMEDICA
/
METABOLISMO
Año:
2019
Tipo del documento:
Article
País de afiliación:
Estados Unidos