1 research outputs found
Development of an Inosine Hyperproducer from Bacillus licheniformis by Systems Metabolic Engineering
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