Pushing Product to Its Limitation: Systems Metabolic Engineering of Corynebacterium Glutamicum for Glutamate Overproduction

Glutamate is a very important amino acid with an annual production of over 2 million tons. Although large efforts have been done to improve its production, the current yield of glutamate by industrial Corynebacterium glutamicum strains is still far from the therotical maximum. In this work, we use genome-scale model to guide the systems metabolic engineering of C.glutamicum for high yield production of glutamate. Main strategies include : 1) increase the precursor availability by enhancement of anaplerotic fluxes and reduction of fluxes towards downstrean TCA pathway; 2) reduction of CO2 emission by modication the fluxes towards pentose phosphate pathway and pyruvate oxidation; 3) introduction of phosphoketolase for acetyl-coA generation; 4) engineering the energy metabolism; 5) engineering glutamate secrete pathway. By combing with media and process optimization, the final engineered strain can produce more than 150 g/L glutamte with the yield ~ 1.0 mol/mol glucose.