Influence of methanol/sorbitol co-feeding rate on pAOX1 induction in a Pichia pastoris Mut+ strain in bioreactor with limited oxygen transfer rate.

摘要: High Pichia pastoris biomass density could be obtained using high co-feeding rate of methanol and sorbitol in a fed-batch or continuous culture, while further higher feeding finally leads to oxygen limitation bioreactor. In the literature, there is lack report about AOX1 promoter regulation with regard dissolved level (DO). Therefore, this work, chemostat cultures were performed investigate cell growth, metabolism (pAOX1) regarding optimized methanol/sorbitol mixture (methanol fraction 0.60 C-mol/C-mol) P. Mut+/pAOX1-lacZ strain. The transfer rates (OTR) bioreactor kept range typical values large bioreactor, i.e., 4-8 g/(L h) if DO equals 30 % saturation 5-10 nears zero. For >0, an increase carbon fed led pAOX1 induction. By contrast, when was completely depleted, accumulated, causing decrease However, more likely lined accumulation than low (<4 DO). Methanol/sorbitol allowed cells adapt transient limitations that often occur at industrial scale reduced effect on optimal tested here 6.6 mmol C (DCW h)(-1) OTR 8.28 g O2(L over fivefold induction (probably directly associated target protein productivity) compared previous work.