초록 |
Corynebacterium glutamicum was engineered for L-arginine production. Random mutagenesis was first performed to increase tolerance to L-arginine. Then, the argR and farR genes encoding the arginine operon repressor proteins were inactivated. The PPP flux was strengthened by downregulating the pgi gene and overexpressing the opcA, pgl, tal, tkt, and zwf genes in an operon. Next, the Ncgl1221 gene encoding L-glutamate exporter was inactivated. Also, the expression levels of the argF and carAB genes were optimized for effective converting L-ornithine to L-citrulline. Finally, the argGH operon was overexpressed to overcome the rate-limiting arginine synthesis. For the large-scale production of L-arginine, fed-batch fermentation of the final strain was performed in a 1,500 L bioreactor resulting 81 g/L of L-arginine production. [This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries (NRF-2012M1A2A2026556) of the Ministry of Education, Science and Technology (MEST) through the National Research Foundation of Korea.] |