Metabolic flux distribution for the optimized production of l-glutamate

Metabolic regulation and overproduction of primary metabolites

“…L-Glutamate titres over 80 g l -1 have been described in the literature (Das et al, 1995;Delaunay et al, 1999). Metabolic engineering approaches have been used to analyse the fermentation (Sonntag et al, 1995;Eggeling et al, 1996;Takac et al, 1998;Kimura, 2003).…”

Metabolic flux analysis for serine alkaline protease fermentation byBacillus licheniformis in a defined medium: Effects of the oxygen transfer rate

“…Also, at higher oxygen transfer rates the cell can waste carbon source and produce excess energy. Vallino and Stephanopoulos (1993) and Takaç et al (1998) also reported high requirements for maintenance throughout the fermentation during lysine and glutamate overproduction, respectively; and they asserted that energy for maintenance calculated as the hydrolysis of ATP did not always reflect the true maintenance energy except during rapid growth and product synthesis periods. According to the approach of Vallino and Stephanopoulos (1993), the values of ATP used for the maintenance (R133), at LOT and MOT conditions in Period I should be higher than that calculated; on the other hand at LOT and MOT conditions in Periods III and IV, and at HOT condition in Period IV should be lower than that calculated.…”

“…Metabolic flux analysis has been successfully applied to a number of fermentation processes (Jorgensen et al, 1995;Papoutsakis and Meyer, 1991;Stephanopoulos and Vallino, 1991;Vallino and Stephanopoulos, 1993;Varma and Palsson, 1995). Although the literature reports on the metabolic flux analysis for two amino acids, L-lysine (Lys) (Hollender 1994;Vallino and Stephanopoulos, 1990, 1994a, 1994b and L-glutamate (Glu) (Pons et al 1996;Takaç et al, 1998) and an antibiotic penicillin V (Jorgensen et al, 1995), there is no related published work involving protease, enzyme, or even protein production. Escherichia coli (Holms, 1986;Varma and Palsson, 1993a, 1993b, Corynebacterium glutamicum (Vallino and Stephanopoulos, 1990, 1994a, 1994b, Corynebacterium melassecola (Pons et al, 1996), Brevibacterium flavum (Takaç et al, 1998), and Penicillium chrysogenum (Jorgensen et al, 1995) were the microorganisms studied for the metabolic flux analysis.…”

On-line optimization of glutamate production based on balanced metabolic control by RQ

“…It is also particularly important in food industries and widely used as an important starting substance for the synthesis of various and useful pharmaceutical and healthy products. The previous research works [2–4] have revealed that primary by-products, such as lactate, accumulated during L -glutamate fermentation if the operating condition was improperly controlled, which in turn deteriorated the fermentation performance in terms of both glutamate productivity and yield.…”

“…To cope with the problem, the metabolic reaction network (flux) model (MR model) or technique, as its appearance in the early 1990s, has been recognized as an useful system analysis tool and thus widely used in those areas such as metabolic flux distribution analysis [2, 5], determination of the bottleneck controlling the targeted metabolic product formation [6, 7], recognition of fermentation phases [8], and calculation of theoretical or maximum yields [9, 10], etc. However, the research reports of using MR model for on-line physiological state prediction or process control are very limited [3, 11, 12], and the study stayed on on-line recognition of different fermentation phases or physiological states so as to provide information for the subsequent process control, such as whether substrate should be added or whether the fermentation should be terminated [11], determination of glucose feeding rate to avoid the acetate or ethanol overproduction in Escherichia coli or Saccharomyces cerevisiae fed-batch cultivation [12], etc.…”