High-level production of γ-aminobutyric acid via efficient co-expression of the key genes of glutamate decarboxylase system in Escherichia coli

通过在大肠杆菌中高效共表达谷氨酸脱羧酶系统的关键基因,实现γ-氨基丁酸的高水平生产

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Abstract

Biosynthesis of the functional factor γ-aminobutyric acid (GABA) in bacteria involves two key proteins an intracellular glutamate decarboxylase (GadB) and a membrane-bound antiporter (GadC). Efficient co-expression of suitable GadB and GadC candidates is crucial for improving GABA productivity. In this study, gadB (ΔC11) of Lactiplantibacillus plantarum and gadC (ΔC41) of Escherichia coli were inserted into the designed double promoter (P (T7lac) and P (BAD) ) expression system. Then, E. coli Lemo21(DE3) was chosen as the host to minimize the toxic effects of GadC(ΔC41) overexpression. Furthermore, a green and high-efficiency GABA synthesis system using dormant engineered Lemo21(DE3) cells as biocatalysts was developed. The total GABA yield reached 829.08 g/L with a 98.7% conversion ratio within 13 h, when engineered E. coli Lemo21(DE3) cells were concentrated to an OD(600) of 20 and reused for three cycles in a 3 M L-glutamate solution at 37 °C, which represented the highest GABA productivity ever reported. Overall, expanding the active pH ranges of GadB and GadC toward physiological pH and employing a tunable expression host for membrane-bound GadC production is a promising strategy for high-level GABA biosynthesis in E. coli.

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