Computer-Based Design of a Cell Factory for High-Yield Cytidine Production.
ACS Synth Biol
; 11(12): 4123-4133, 2022 12 16.
Article
em En
| MEDLINE
| ID: mdl-36442151
ABSTRACT
Pyrimidine ribonucleotide de novo biosynthesis pathway (PRdnBP) is an important pathway to produce pyrimidine nucleosides. We attempted to systematically investigate PRdnBP in Escherichia coli with genome-scale metabolic models and utilized the models to guide strain design. The balance of central carbon metabolism and PRdnBP affected the production of cytidine from glucose. Using Bayesian metabolic flux analysis, the effect of modified PRdnBP on the metabolic network was analyzed. The acetate overflow became coupled with PRdnBP flux, while they were originally independent under oxygen-sufficient conditions. The coupling between cytidine production and acetate secretion in the modified strain was weakened by arcA deletion, which resulted in further improving the efficient accumulation of cytidine. In total, 1.28 g/L of cytidine with a yield of 0.26 g/g glucose was produced. The yield of cytidine produced by E. coli is higher than previous reports. Our strategy provides an effective attempt to find metabolic bottlenecks in genetically engineered bacteria by using flux coupling analysis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citidina
/
Escherichia coli
Tipo de estudo:
Prognostic_studies
Idioma:
En
Revista:
ACS Synth Biol
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
China