Efficient production of guanosine in Escherichia coli by combinatorial metabolic engineering.
Microb Cell Fact
; 23(1): 182, 2024 Jun 19.
Article
en En
| MEDLINE
| ID: mdl-38898430
ABSTRACT
BACKGROUND:
Guanosine is a purine nucleoside that is widely used as a raw material for food additives and pharmaceutical products. Microbial fermentation is the main production method of guanosine. However, the guanosine-producing strains possess multiple metabolic pathway interactions and complex regulatory mechanisms. The lack of strains with efficiently producing-guanosine greatly limited industrial application.RESULTS:
We attempted to efficiently produce guanosine in Escherichia coli using systematic metabolic engineering. First, we overexpressed the purine synthesis pathway from Bacillus subtilis and the prs gene, and deleted three genes involved in guanosine catabolism to increase guanosine accumulation. Subsequently, we attenuated purA expression and eliminated feedback and transcription dual inhibition. Then, we modified the metabolic flux of the glycolysis and Entner-Doudoroff (ED) pathways and performed redox cofactors rebalancing. Finally, transporter engineering and enhancing the guanosine synthesis pathway further increased the guanosine titre to 134.9 mg/L. After 72 h of the fed-batch fermentation in shake-flask, the guanosine titre achieved 289.8 mg/L.CONCLUSIONS:
Our results reveal that the guanosine synthesis pathway was successfully optimized by combinatorial metabolic engineering, which could be applicable to the efficient synthesis of other nucleoside products.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Escherichia coli
/
Fermentación
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Ingeniería Metabólica
/
Guanosina
Idioma:
En
Revista:
Microb Cell Fact
Asunto de la revista:
BIOTECNOLOGIA
/
MICROBIOLOGIA
Año:
2024
Tipo del documento:
Article
País de afiliación:
China