L-Phenylalanine Production in Continuous Culture Using a Hyperproducing Mutant of Escherichia Coli K-12

Park, N.H.; Rogers, Peter L.

doi:10.1080/00986448608911382

Cited by 16 publications

(4 citation statements)

References 13 publications

(10 reference statements)

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“…Co-expression of enzymes was carried out with Escherichia coli or Candida boidinii [6] and homologue bioconversion from phenylpyruvate to L-Phe by resting [7], immobilised [8], or growing E. coli [9,10] or Corynebacterium glutamicum cells [11,12]. Fermentation processes have been developed and optimised for mutants or genetically engineered from strains of C. glutamicum [35,36,37], Brevibacterium lactofermentum [38], Bacillus sublitis [39] or B. flavum [40] and especially of E. coli [13,14,15,16,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34].…”

Section: Introductionmentioning

confidence: 99%

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Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction

Maass

et al. 2002

Bioprocess and Biosystems Engineering

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A fully integrated process for the microbial production and recovery of the aromatic amino acid L-phenylalanine is presented. Using a recombinant L-tyrosine (L-Tyr) auxotrophic Escherichia coli production strain, a fed-batch fermentation process was developed in a 20-l-scale bioreactor. Concentrations of glucose and L-Tyr were closed-loop-controlled in a fed-batch process. After achieving final L-phenylalanine (L-Phe) titres >30 g/l the process strategy was scaled up to 300-l pilot scale. In technical scale fermentation L-phenylalanine was continuously recovered via a fully integrated reactive extraction system achieving a maximum extraction rate of 110 g/h (final purity >99%). It was thus possible to increase L-Phe/glucose selectivity from 15 mol% without to 20.3 mol% with integrated product separation.

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Section: Introductionmentioning

confidence: 99%

“…Considerable progress has been made to convert E. coli into an organism suited for L-Phe production [20,25,29]. For industrial process development, E. coli offers the advantages of high growth and production rates combined with high yields using simple defined media which are suitable for efficient product recovery.…”

Section: Introductionmentioning

confidence: 99%

Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction

Maass

et al. 2002

Bioprocess and Biosystems Engineering

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“…L-phenylalanine, 16 L-arginine,2 and ~-1ysine.~~"~~' Continuous amino acid processes are generally more difficult to maintain than * To whom all correspondence should be addressed. Less work has been done with amino acid fermentations in continuous culture.…”

Section: Introductionmentioning

confidence: 99%

Culture instability of auxotrophic amino acid producers

Kiss

Stephanopoulos

1992

Biotech & Bioengineering

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The long-term dynamic characteristics of the L-lysine producer Corynebcterium glutamicum in continuous culture were studied over a range of specific growth rates. The double-auxotroph parent strain was found to be susceptible to a back mutation, or reversion, which negated the regulatory bypass that allows this strain to accumulate L-lysine in culture but also gives rise to a L-threonine auxotrophic requirement. Consequently, the revertant cells no longer over-produced L-lysine, nor were they limited in their growth by the low levels of L-threonine in the medium. All continuous culture experiments were eventually taken over by these revertants. The instability of the culture was found to be primarily due to the growth rate differential between the two competing populations, the (productive) parent auxotrophs and the (nonproductive) revertants. A deterministic mathematical model of the culture dynamics, incoroporating two limiting-substrate balances, satisfactorily described the takeover profiles. A linear stability analysis of the model equations identified that although long-term culture demise is inevitable, the dimensionless ratio of the two limiting substrates controls the rate of takeover by nonproductive cells. The analysis further demonstrated the importance of proper medium design in delaying the onset of takeover in cultures of this double-auxotroph strain. The theoretical medium design criterion was then confirmed experimentally by the stabilization of a fed-batch culture against revertant takeover for an extended fermentation time.

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“…Although there have been many reports on continuous culture, most of them have been concerned with the fermentative production of single cell protein, organic acid or alcohol (Srinivasan and Summers 1981). Few attempts have been made to produce amino acids in continuous culture (Mimura et al 1963;Choi and Tribe 1982;Park and Rogers 1986).…”

Section: Introductionmentioning

confidence: 99%

l-Lysine production in continuous culture of an l-lysine hyperproducing mutant of Corynebacterium glutamicum

Hirao

Nakano

Azuma

et al. 1989

Appl Microbiol Biotechnol

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L-Lysine production was studied in continuous culture with a single-stage cultivation process using the L-lysine hyperproducing mutant B-6 of Corynebacterium glutamicum. showed stable L-lysine production for over 500 h.The maximum values of L-lysine-HC1 concentration and volumetric productivity were 105 g/1 and 5.6 g/1 per hour, respectively. The latter corresponded to a 2.5-fold higher value than that of a fed-batch culture. Higher agitation or use of oxygen-enriched air was critical for high productivity. This indicates that oxygen supply greatly affects L-lysine productivity in continuous culture.

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L-Phenylalanine Production in Continuous Culture Using a Hyperproducing Mutant of Escherichia Coli K-12

Cited by 16 publications

References 13 publications

Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction

Enhanced pilot-scale fed-batch L-phenylalanine production with recombinant Escherichia coli by fully integrated reactive extraction

Culture instability of auxotrophic amino acid producers

l-Lysine production in continuous culture of an l-lysine hyperproducing mutant of Corynebacterium glutamicum

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