A hybrid Embden–Meyerhof–Parnas pathway provides a synthetic link between sugar and phosphate metabolism
AbstractThe fundamental Embden–Meyerhoff–Paranas (EMP) pathway for sugar catabolism, anabolism, and energy metabolism has been reconstituted with non-oxidative glycolysis (NOG). Although carbon conservation was achieved via NOG, the energy metabolism was significantly limited. Herein, we showed the construction of a hybrid EMP that replaced the first phase of the EMP in Corynebacterium glutamicum with NOG and revealed a metabolic link of carbon and phosphorus metabolism. In accordance with synthetic glucose kinase activity and phosphoketolase on the hybrid EMP, cell growth was completely recovered in the C. glutamicum pfkA mutant strain where the first phase of EMP was eliminated. Notably, we have revealed a phosphate-replenishing pathway that involved trehalose biosynthesis for the generation of inorganic phosphate (Pi) sources in the hybrid EMP when external Pi supply was limited. Thus, the re-designed hybrid EMP pathway with balanced carbon and phosphorus states provides an efficient microbial platform for biochemical production.