Metabolic engineering of cyanobacteria for the photosynthetic production of succinate

Abstract

Succinate is an important commodity chemical currently used in the food, pharmaceutical, and polymer industries. It can also be chemically converted into other major industrial chemicals such as 1,4-butanediol, butadiene, and tetrahydrofuran. Here we metabolically engineered a model cyanobacterium Synechococcus elongatus PCC 7942 to photosynthetically produce succinate. We expressed the genes encoding for α-ketoglutarate decarboxylase and succinate semialdehyde dehydrogenase in S. elongatus PCC 7942, resulting in a strain capable of producing 120mg/L of succinate. However, this recombinant strain exhibited severe growth retardation upon induction of the genes encoding for the succinate producing pathway, potentially due to the depletion of α-ketoglutarate. To replenish α-ketoglutarate, we expressed the genes encoding for phosphoenolpyruvate carboxylase and citrate synthase from Corynebacterium glutamicum into the succinate producing strain. The resulting strain successfully restored the growth phenotype and produced succinate with a titer of 430mg/L in 8 days. These results demonstrated the possibility of photoautotrophic succinate production.