Development of an Inosine Hyperproducer from Bacillus licheniformis by Systems Metabolic Engineering.
J Agric Food Chem
; 71(50): 20210-20221, 2023 Dec 20.
Article
em En
| MEDLINE
| ID: mdl-38079219
ABSTRACT
Inosine is widely used in food, chemical, and medicine. This study developed Bacillus licheniformis into an inosine hyperproducer through systems metabolic engineering. First, purine metabolism was activated by deleting inhibitors PurR and YabJ and overexpressing the pur operon. Then, the 5-phosphoribosyl-1-pyrophosphate (PRPP) supply was increased by optimizing the glucose transport system and pentose phosphate pathway, increasing the inosine titer by 97% and decreasing the titers of byproducts by 36%. Next, to prevent the degradation of inosine, genes deoD and pupG coding purine nucleoside phosphorylase were deleted, accumulating 0.91 g/L inosine in the culture medium. Additionally, the downregulation of adenosine 5'-monophosphate (AMP) synthesis pathway increased the inosine titer by 409%. Importantly, enhancing the glycine and aspartate supply increased the inosine titer by 298%. Finally, the guanosine synthesis pathway was blocked, leading to strain IR-8-2 producing 27.41 g/L inosine with a 0.46 g inosine/g glucose yield and a 0.38 g/(L·h) productivity in a shake flask.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Bacillus licheniformis
Idioma:
En
Revista:
J Agric Food Chem
Ano de publicação:
2023
Tipo de documento:
Article