Increasing pentose phosphate pathway flux enhances recombinant protein production in Pichia pastoris

摘要: Production of heterologous proteins in Pichia pastoris (syn. Komagataella sp.) has been shown to exert a metabolic burden on the host metabolism. This is associated with metabolite drain, which redirects nucleotides and amino acids from primary On other hand, recombinant protein production affects energy redox homeostasis cell. In previous study, we have demonstrated that overexpression single genes oxidative pentose phosphate pathway (PPP) had positive influence cytosolic human superoxide dismutase (hSOD). this different combinations these belonging PPP were generated analyzed. Thereby, 3.8-fold increase hSOD was detected when glucose-6-phosphate dehydrogenase (ZWF1) 6-gluconolactonase (SOL3) simultaneously overexpressed, while no effect production. By measuring isotopologue patterns (13)C-labelled metabolites, could detect an upshift flux ratio glycolysis upon ZWF1 SOL3 co-overexpression, as well increased levels 6-phosphogluconate. The substantial improvement by co-overexpression appeared be connected flux. conclusion, show together enhanced both accumulation, providing evidence P. Sol3 limits through