Systems Metabolic Engineering to Elucidate and Enhance Intestinal Metabolic Activities of Escherichia coli Nissle 1917

Escherichia coli Nissle
1917 (EcN)
is one of the most widely used probiotics to treat gastrointestinal
diseases. Recently, many studies have engineered EcN to release therapeutic
proteins to treat specific diseases. However, because EcN exhibits
intestinal metabolic activities, it is difficult to predict outcomes
after administration. In silico and fermentation
profiles revealed mucin metabolism of EcN. Multiomics revealed that
fucose metabolism contributes to the intestinal colonization of EcN
by enhancing the synthesis of flagella and nutrient uptake. The multiomics
results also revealed that excessive intracellular trehalose synthesis
in EcN, which is responsible for galactose metabolism, acts as a metabolic
bottleneck, adversely affecting growth. To improve the ability of
EcN to metabolize galactose, otsAB genes for trehalose
synthesis were deleted, resulting in the ΔotsAB strain; the ΔotsAB strain exhibited a 1.47-fold
increase in the growth rate and a 1.37-fold increase in the substrate
consumption rate relative to wild-type EcN.