Optimization of L‐phenylalanine production of Corynebacterium glutamicum under product feedback inhibition by elevated oxygen transfer rate

Abstract

Production feedback inhibition both on cell growth and on product formation of phenylalanine fermentation might be alleviated by elevated oxygen supply. Batch fermentations by a high phenylalanine producing strain Corynebacterium glutamicum CCRC 18335 at various initial phenylalanine concentrations (P(0)) ranging from 0 to 20 g/L and different oxygen transfer rate coefficients (K(L)a) ranging from 23 to 76 h(-1) were studied. The fermentation parameters with respect to P(0) were strongly dependent on K(L)a. Cell yield favored higher K(L)a and lower P(0). Product yield with respect to varying phenylalanine concentration was evaluated by the relative oxygen availability (ROA). The optimal ROA for phenylalanine formation was strongly dependent on the product concentration. While P(0) was low, the product inhibition was less significant and the maximum product yield occurred while ROA was at 0.5-0.6. While P(0) was high, the product inhibition was significant and the maximum product yield occurred while ROA was at 0.8-0.9. These results suggest that the product feedback inhibition of phenylalanine fermentation processes can be alleviated by a gradual increase in oxygen supply rate while the increasing product concentration is taken into account. The strategy is demonstrated in a fed-batch culture with elevated oxygen supply. The final phenylalanine concentration was 23.2 g/L, which was 45% better than that of the fed-batch fermentation without elevated oxygen supply. Likewise, the maximum productivity was improved by 42% at 0.37 g/(L x h).

Production of l-phenylalanine from glycerol by a recombinant Escherichia coli

“…Attaining such a high concentration inevitably requires a fed-batch fermentation process. Mixed carbon sources involving predominantly but not exclusively glycerol have been used to produce L-phenylalanine in highly aerobic fed-batch cultures of Corynebacterium glutamicum [24]. A Wnal product concentration of nearly 23 g L ¡1 and a productivity of 0.32 g L ¡1 h ¡1 were reported in an extensively optimized fed-batch fermentation [24].…”

Fully integrated L-phenylalanine separation and concentration using reactive-extraction with liquid-liquid centrifuges in a fed-batch process with E. coli

“…Therefore, numerous studies have already been performed focusing, for instance, on L-phe production with isolated enzymes [5,6,7,8], immobilized cells [9] or resting cells [10]. Fermentation processes have also been investigated using Corynebacterium glutamicum [11,12,13] or, most importantly, Escherichia coli [14,15,16,17,18,19].…”

Dynamic Modeling of Apoptosis and its Interaction with Cell Growth in Mammalian Cell Culture

“…To confirm that growth arrest was not related to oxygen depletion, dissolved oxygen was measured during the experiments. The dissolved oxygen in all the cultures ranged between 40-80% (Figure 7.3), which is sufficient for the cell growth and not in the limiting range that can lead to conditions of hypoxia (Ozturk and Palsson, 1990b;Shu and Liao, 2002;Trummer et al, 2006). Figure 7.4A shows the time evolution of mAb concentration in each different volume.…”