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The efficiency of industrial fermentation process mainly depends on carbon yield, final titer and productivity. To improve the efficiency of  l -lysine production from mixed sugar, we engineered carbohydrate metabolism systems to enhance the effective use of sugar in this study. A functional metabolic pathway of sucrose and fructose was engineered through introduction of fructokinase from  Clostridium acetobutylicum .  l -lysine production was further increased through replacement of phosphoenolpyruvate-dependent glucose and fructose uptake system (PTS Glc  and PTS Fru ) by inositol permeases (IolT1 and IolT2) and ATP-dependent glucokinase (ATP-GlK). However, the shortage of intracellular ATP has a significantly negative impact on sugar consumption rate, cell growth and  l -lysine production. To overcome this defect, the recombinant strain was modified to co-express bifunctional ADP-dependent glucokinase (ADP-GlK/PFK) and NADH dehydrogenase (NDH-2) as well as to inactivate SigmaH factor (SigH), thus reducing the consumption of ATP and increasing ATP regeneration. Combination of these genetic modifications resulted in an engineered  C. glutamicum  strain K-8 capable of producing 221.3 ± 17.6 g/L  l -lysine with productivity of 5.53 g/L/h and carbon yield of 0.71 g/g glucose in fed-batch fermentation. As far as we know, this is the best efficiency of  l -lysine production from mixed sugar. This is also the first report for improving the efficiency of  l -lysine production by systematic modification of carbohydrate metabolism systems.

microbial cell factories

Metabolic engineering of carbohydrate metabolism systems in Corynebacterium glutamicum for improving the efficiency of l-lysine production from mixed sugar