<P><B>Abstract</B></P> <P>Poor high salt stress resistance remained as a main hurdle limiting the efficient bio-based succinic acid production. In this study, the metabolically engineered <I>E. coli</I> not only showed improvement of high salt stress tolerance through expression of a global regulator IrrE, but also could use seawater for succinic acid fermentation. The recombinant strain showed an increased 1.20-fold of cell growth rate and 1.24-fold of succinic acid production. Expression levels of genes related glucose uptake and succinic acid synthesis were up-regulated, and more glycerol and trehalose were accumulated. Moreover, no significant differences were observed in cell growth even when tap water was replaced by 60% artificial seawater. In the fermentation using Yellow Sea seawater, 24.5 g/L succinic acid was achieved with a yield of 0.88 g/g. This strategy set up a platform for improving abiotic stress tolerances and provide a possible approach for fermentation processes with low cost.</P> <P><B>Highlights</B></P> <P> <UL> <LI> IrrE improve high salt tolerance and succinic acid production in <I>E. coli</I>. </LI> <LI> IrrE may function by regulating genes involved in metabolic pathway. </LI> <LI> Seawater was used as alternative water source for succinic acid fermentation. </LI> <LI> A 24.5 g/L of succinic acid titer with a yield of 0.88 g/g was achieved in seawater. </LI> </UL> </P>