Enhancement of α-ketoglutarate production in Torulopsis glabrata: Redistribution of carbon flux from pyruvate to α-ketoglutarate

This manuscript aimed at increasing the production of α-ketoglutarate by the multi-vitamin auxotrophic yeast Torulopsis glabrata CCTCC M202019. The carbon flux was redistributed from pyruvate to α-ketoglutarate node by manipulating the specific activity of pyruvate dehydrogenase complex (PDH), pyruvate carboxylase (PC), pyruvate decarboxylase (PDC), and α-ketoglutarate dehydrogenase complex (KGDH). By proper increase of PDH, PC, and PDC activities, α-ketoglutarate in fermentation broth could be accumulated to the levels of 17.1 g/L, 21.6 g/L, and 31.2 g/L, respectively. In addition, decrease in the specific activity of KGDH also resulted in an enhanced α-ketoglutarate synthesis. With a proposed combinational enzymes regulation strategy, the highest α-ketoglutarate concentration of 37.7 g/L was achieved.