Intracellular redox manipulation of Zymomonas mobilis for improving tolerance against lignocellulose hydrolysate-derived stress

[Display omitted] •Redox manipulation improved the inhibitor tolerance of Zymomonas mobilis ZM4.•Removing ROS and supplying ATP enhanced cell growth under inhibitors stress.•Z. mobilis showed metabolic burden even under the modest co-factor disturbance.•Metabolic burden and inhibitor concentrations affect the tolerance-related genes. The lignocellulose hydrolysate-derived inhibitors compromise the cell growth and fermentation. In this study, intracellular redox potential was manipulated by overexpressing eight genes encoding cofactors-related oxidoreductases to improve the tolerance of Zymomonas mobilis ZM4 to lignocellulose hydrolysate-derived inhibitors. Besides, the underlying mechanism was elucidated through monitoring the cellular redox balance including NAD(P)H/NAD(P)+, ROS, and ATP. The oxidoreductases either directly degraded furfural or provided NAD(P)H for reducing it under furfural stress. Whereas, the elevated ratio of NADPH/NADP+ strengthened the tolerance against acetate via removing ROS and supplying ATP. The enzymes benefiting ATP accumulation also enhanced cell growth under formate stress. It is concluded that concentration of inhibitors and metabolic burden both contribute stress tolerance of Z. mobilis. The data here projected a comprehensive approach to developing multi-stress tolerance strategy in industrially valuable strains to produce biofuels and biochemicals from lignocellulosic biomass.