BACKGROUNDCorynebacterium glutamicum was engineered for improvement of L-lysine production and minimization of by-products synthesis by genetically engineering. RESULTSThe most promising recombinant strain C. glutamicum Lys9 produced 62.1 mmol L-1 L-lysine with substrate-specific yield (Y-P/S) of 0.28 mol per mol of glucose in shake flasks fermentation, whereas parental strain showed more than four times lower L-lysine production and more than 10 times lower biomass-specific yield (Y-P/X) than that of C. glutamicum Lys9. L-lysine production and cell growth were drastically decreased by isocitrate dehydrogenase (ICD) attenuation in aceE deletion strains, indicating that down-regulation of ICD activity in aceE deletion strains adversely affects L-lysine production. In fed-batch fermentation, C. glutamicum Lys9 produced 526 mmol L-1 L-lysine, i.e. 96.8 g L-1 L-lysine-HCl with high yield of 0.422 mol per mol of glucose and productivity of 2.69 g L-1 h(-1). Corynebacterium glutamicum Lys9 was devoid of any detectable L-alanine and L-lactate synthesis. CONCLUSIONSuperior to classical producers to some degree, C. glutamicum Lys9 is more adaptable for industrial L-lysine production. In addition to L-lysine, pyruvate, oxaloacetate (OAA) and L-valine were produced by C. glutamicum Lys9, suggesting further optimization to improve L-lysine production by engineering the L-lysine and/or NADPH biosynthetic pathway. (c) 2013 Society of Chemical Industry