초록 |
Industrial amino acids powerhouse Corynebacterium glutamicum was engineered for L-arginine production. First, random mutagenesis was performed on C. glutamicum to increase tolerance to L-arginine. Next, the arginine operon repressor proteins argR and farR were inactivated. By downregulating the pgi gene and overexpressing the opcA, pgl, tal, tkt, and zwf genes, PPP flux was strengthened. Subsequently, the Ncgl1221 gene encoding L-glutamate exporter was inactivated to channel L-glutamate to L-arginine. In addition, argF and carAB gene expression levels were optimized to convert L-ornithine to L-citrulline. Finally, the argGH operon was overexpressed. Fed-batch fermentation of the final strain in a 1,500 L bioreactor resulted in 81 g/L of L-arginine production. The approaches described here will be useful in developing microbes for the production of arginine and its derivatives. [This work was supported by the Technology Development Program to Solve Climate Changes on Systems Metabolic Engineering for Biorefineries from the Ministry of Science, ICT and Future Planning (MSIP) through the National Research Foundation (NRF) of Korea (NRF-2012M1A2A2026556 and NRF-2012M1A2A2026557)] |