The fermentation process for l-phenylalanine production using an auxotrophic regulatory mutant of Escherichia coli

Hwang, Sungwon; Gil, Gwang Hoon; Cho, Y. J.; Kang, Kyoung-Hee; Lee, J. H.; Bae, Jong Chan

doi:10.1007/bf00250029

Cited by 36 publications

(13 citation statements)

References 9 publications

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“…These ®ndings indicate that the biosynthetic enzymes of phenylalanine are not deregulated completely in these mutants and recombinants, which becomes the major factor limiting end-product accumulation. This might also explain the results of several investigations, in which the maximum phenylalanine concentrations were less than 17 g/L even though their processes were optimized by oxygen supply rate control (Akashi et al, 1979a), glucose feeding strategy (Hwang et al, 1985), and phosphate limitation control (Choi and Tribe, 1982).…”

Section: Introductionmentioning

confidence: 92%

“…Along with the progress of strain improvement, various fermentation strategies have been developed to improve phenylalanine concentration and volumetric productivity, including oxygen supply rate control (Akashi et al, 1979a;Konstantinov et al, 1991), glucose feeding rate (Choi and Tribe, 1982;Forberg et al, 1988;Hwang et al, 1985;Takagi et al, 1996), temperature (Sugimoto et al, 1990), and non-growing culture (Weikert et al, 1998). Although end-product removal techniques are common solutions used to enhance product yields whenever product inhibition is present, only rarely have attempts succeeded in phenylalanine fermentation process.…”

Section: Introductionmentioning

confidence: 99%

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

Shu

Liao

2001

Biotech & Bioengineering

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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).

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Section: Introductionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

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

Shu

Liao

2001

Biotech & Bioengineering

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“…Telephone: 8 1-6-879-7455: fax: 81-6-879-7454 it requires a large energy input and the productivity is generally not high. As a result of several investigations, the phenylalanine concentration, production rate, and product yield based on the amount of glucose consumed were improved to 17 g/L, 0.3 g/L/h, and 13%, respectively (Akashi et al, 1979;Choi and Tribe, Forberg et al, 1988;Hwang et al, 1985).…”

Section: Introductionmentioning

confidence: 96%

Control of L-phenylalanine production by dual feeding of glucose and L-tyrosine

Takagi

Nishio

et al. 2000

Biotechnol. Bioeng.

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“…Beyond several approaches using isolated enzymes (Asano et al, 1987;Hummel et al, 1987;Nakamichi et al, 1989;Ziehr et al, 1987), resting cells , or immobilized cells (patent Wood and Calton, US-A-4728611, 1988), fermentation process development mainly focused on E. coli (Backman et al, 1989;Choi and Tribe, 1982;Gerigk et al, 2002;Grinter, 1998;Hwang et al, 1985;Park and Rogers, 1988;Maass et al, 2001 (in press, Bioprocess and Biosystems Engineering); Sugimoto et al, 1990;Weikert et al, 1998) leading to several patent applications (Kim et al, US-A-5304475, 1994;Lee et al, US-A-5008190, 1991;Lim et al, US-A-5409830, 1995;Sprenger et al, WO-98/18937, 1998).…”

Section: Introductionmentioning

confidence: 99%

Process control for enhanced L‐phenylalanine production using different recombinant Escherichia coli strains

Gerigk¹,

Bujnicki²,

Ganpo-Nkwenkwa³

et al. 2002

Biotech & Bioengineering

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A novel fed-batch approach for the production of L-phenylalanine (L-Phe) with recombinant E. coli is presented concerning the on-line control of the key fermentation parameters glucose and tyrosine. Two different production strains possessing either the tyrosine feedback resistant aroF(fbr) (encoding tyrosine feedback resistant DAHP-synthase (3-desoxy-D-arabino-heptusonate-7-phosphate)) or the wild-type aroF(wt) were used as model systems to elucidate the necessity of finding an individual process optimum for each genotype. With the aid of tyrosine control, wild-type aroF(wt) could be used for L-Phe production achieving higher final L-Phe titers (34 g/L) than the aroF(fbr) strain (28 g/L) and providing higher DAHP-synthase activities. With on-line glucose control, an optimum glucose concentration of 5 g/L could be identified that allowed a sufficient carbon supply for L-Phe production while at the same time an overflow metabolism leading to acetate by-product formation was avoided. The process approach is suitable for other production strains not only in lab-scale but also in pilot-scale bioreactors.

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The fermentation process for l-phenylalanine production using an auxotrophic regulatory mutant of Escherichia coli

Cited by 36 publications

References 9 publications

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

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

Control of L-phenylalanine production by dual feeding of glucose and L-tyrosine

Process control for enhanced L‐phenylalanine production using different recombinant Escherichia coli strains

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