Improvement of l-arginine production by in silico genome-scale metabolic network model guided genetic engineering

Genome-scale metabolic network model (GSMM) is an important in silico tool that can efficiently predict the target genes to be modulated. A Corynebacterium crenatum argB-M4 Cc_iKK446_arginine model was constructed on the basis of the GSMM of Corynebacterium glutamicum ATCC 13032 Cg_iKK446. Sixty-four gene deletion sites, twenty-four gene enhancement sites, and seven gene attenuation sites were determined for the improvement of l-arginine production in engineered C. crenatum. Among these sites, the effects of disrupting putP, cgl2310, pta, and Ncgl1221 and overexpressing lysE on l-arginine production were investigated. Moreover, the strain CCM007 with deleted putP, cgl2310, pta, and Ncgl1221 and overexpressed lysE produced 24.85 g/L l-arginine. This finding indicated a 106.8% improvement in l-arginine production compared with that in CCM01. GSMM is an excellent tool for identifying target genes to promote l-arginine accumulation in engineered C. crenatum.