Overexpression of the Key Enzymes in the Methylerythritol 4-phosphate Pathway in Corynebacterium glutamicum for Improving Farnesyl Diphosphate-Derived Terpene Production.

Hyeonbae Lim, Jaehyun Park, Han Min Woo

Journal of agricultural and food chemistry 2020 Sep 30

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A systematic and combinatorial optimization has been employed to metabolically engineer microbes for identifying key gene targets for overexpression to increase the intermediate pools for terpenoid production. Herein, the methylerythritol 4-phosphate (MEP) pathway in Corynebacterium glutamicum, an industrial host, was investigated to identify the key genes whose overexpression would improve the production of farnesyl diphosphate (FPP)-derived terpenoids (squalene and α-farnesene). Using a combinatorial approach with the single, double, and triple expression of genes in the MEP pathway in a high-throughput fermentation, overexpression of the ispDF genes, along with the known dxs and idi genes, was most effective at increasing the squalene contents, i.e., by 14-fold. The dxr gene was identified as the key target enzyme for α-farnesene production. This result could provide fundamental information for improving the metabolic engineering of C. glutamicum for terpene production via an optimized MEP pathway.

Citation

Hyeonbae Lim, Jaehyun Park, Han Min Woo. Overexpression of the Key Enzymes in the Methylerythritol 4-phosphate Pathway in Corynebacterium glutamicum for Improving Farnesyl Diphosphate-Derived Terpene Production. Journal of agricultural and food chemistry. 2020 Sep 30;68(39):10780-10786