Improving glutarate production in Escherichia coli by enhancing the CoA
precursors
Abstract
Glutarate is an attractive C5 platform chemical having wide application
in nylon and plasticizer. However, microbial glutarate is mainly
accumulated in the degradation of lysine and other methods were rarely
explored for producing the glutarate from glucose directly. Here, we
utilized a reversed adipic acid degradation pathway (RADP) and improved
the glutarate production by increasing the precursors (malonyl-CoA and
acetyl-CoA) based on the previously studied strain Bgl4146.
Specifically, the conversion system of intracellular acetyl-CoA to
malonyl-CoA was firstly constructed and optimized to balance acetyl-CoA
synthase and acetyl-CoA carboxylase under different dissolved oxygen,
enhancing the glutarate production from 0.09 g/L to 0.49 g/L. Then,
modulating CoA balance by monitoring the expression of acetate kinase
and pyruvate dehydrogenase resulting in a rise in glutarate titer up to
0.70 g/L. Finally, the optimized strain Bgl51464 was able to produce
7.97 g/L glutarate in a 5-L bioreactor. This strategy was described
here, which could lay a certain foundation for the development of
effective CoA balance to produce industrially high value-added
chemicals.