A pyruvate-centered metabolic regulation mechanism for the enhanced expression of exogenous genes in Escherichia coli

A novel Escherichia coli efficient expression system had been constructed in our previous study. The system was based on the overexpression of endogenous genes prpD and malK to enhance the expression of exogenous genes. In this study, a general regulatory mechanism of prpD and malK was first revealed through transcriptome analysis and many experimental verifications. We surprisingly proved that overexpression of malK could up-regulate the expression of prpD and propanoate metabolism, which leads to increased expression of exogenous genes. More importantly, the overexpression of prpD or malK could arouse a complex set of pyruvate-centered metabolic networks that mainly increase the energy supply (ATP), by-product recycling (acetate), and amino acids for the efficient expression of exogenous genes. This novel theory for promoting the efficient expression of exogenous genes will be useful in a wide range of fields. It also opens up a new perspective on the regulation of metabolism in E. coli cells.