Adaptive Control Strategy for Maintaining Dissolved Oxygen Concentration in High Density Growth of Recombinant <i>E. coli</i>

Hsiao, Jason; Ahluwali, Mo; Kaufman, Joyce J.; Clem, Thomas R.; Shiloach, Joseph

doi:10.1111/j.1749-6632.1992.tb42595.x

Cited by 27 publications

(13 citation statements)

References 15 publications

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“…After sterilization, 10 mM MgSO 4 , 1 mL trace metal solution, 0.6 g thiamine (DH5a) and glucose or glycerol to final concentration of 5 g/L were added. The fermentor was inoculated with 200 mL of overnight culture and was cultivated in batch mode at 308C; pH 7, and 30% dissolved oxygen concentration maintained by adaptive controlled system adjusting agitation rate and air or oxygen flow rate (Hsiao et al, 1992). After approximately 4 h (OD 600 nm $10), fed-batch mode based on dissolved oxygen set point of 30% was implemented by using Yokogawa model UT152 controller and a Watson Mallow pump delivering 6 mL per dose of 50% glycerol or glucose feeding solution containing 25% yeast extract, 10 mM MgSO 4 , 1 mL/mL trace metal solution and 0.6 g thiamine (DH5a).…”

Section: Fermentationmentioning

confidence: 99%

Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5α)

Phue

Lee²,

Trinh

et al. 2008

Biotech & Bioengineering

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Plasmid DNA (pDNA) is an emerging experimental vaccine, produced in E. coli, initially targeted for viral diseases. Unlike traditional protein vaccines whose average dose is micrograms, the average dose of pDNA is on the scale of milligrams. Production yields are, therefore, important for the future development of this vaccine. The E. coli strains currently used for pDNA production, JM109 and DH5alpha, are both suitable for production of stable pDNA due to the deletion of recA and endA, however, these two E. coli K strains are sensitive to growth conditions such as high glucose concentration. On the other hand E. coli BL21 is less sensitive to growth conditions than E. coli JM109 or DH5alpha, this strain grows to higher densities and due to its active glyoxylate shunt and anaplerotic pathways is not sensitive to high glucose concentration. This strain is used for recombinant protein production but not for pDNA production because of its inability to produce stable pDNA. To adapt E. coli BL21 for stable pDNA production, the strain was mutated by deleting both recA and endA, and a proper growth and production strategy was developed. Production values, reaching 2 g/L were obtained using glucose as a carbon source. The produced plasmid, which was constructed for HIV clinical study, was found to have identical properties to the plasmid currently produced by E. coli DH5alpha.

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Section: Fermentationmentioning

confidence: 99%

Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5α)

Phue

Lee²,

Trinh

et al. 2008

Biotech & Bioengineering

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“…Bench-top fermentation was performed in a 7-L fermentor (New Brunswick Scientific, Edison, NJ) The fermentor is interfaced to an MD-Biostat System (B. Braun Biotech USA, Allentown, PA) furnished with an adaptive control algorithm (Hsiao et al, 1992) that maintained dissolved oxygen at 30% saturation by adjusting the agitation and air or oxygen. The fermentor was also equipped with a methanol sensor (Trinh et al, 2000;Wagner et al, 1997).…”

Section: Yeast Strain and Fermentation Processesmentioning

confidence: 99%

Effect of methanol feeding strategies on production and yield of recombinant mouse endostatin from Pichia pastoris

Trinh

Phue²,

Shiloach

2003

Biotech & Bioengineering

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Pichia pastoris, a methylotrophic yeast, is an efficient producer of recombinant proteins in which the heterologous gene is under the control of the methanol-induced AOX1 promoter. Hence, the accepted production procedure has two phases: In the first phase, the yeast utilizes glycerol and biomass is accumulated; in the second phase, the yeast utilizes methanol which is used both as an inducer for the expression of the recombinant protein and as a carbon source. Since the yeast is sensitive to methanol concentration, the methanol is supplied gradually to the growing culture. Three methanol addition strategies were evaluated for the purpose of optimizing recombinant endostatin production. Two strategies were based on the yeast metabolism; one responding to the methanol consumption using a methanol sensor, and the other responding to the oxygen consumption. In these two strategies, the methanol supply is unlimited. The third strategy was based on a predetermined exponential feeding rate, controling the growth rate at 0.02 h(-1), in this strategy the methanol supply is limited. Throughout the induction phase glycerol, in addition to methanol, was continuously added at a rate of 1 g L h(-1). Total endostatin production was similar in all three strategies, (400 mg was obtained from 3 L initial volume), but the amount of methanol added and the biomass produced were lower in the predetermined rate method. This caused the specific production of endostatin per biomass and per methanol to be 2 times higher in the predetermined rate than in the other two methods, making the growth control strategy not only more efficient but also more convenient for downstream processing.

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“…The parameters of this model were estimated on-line and used by a one-step ahead controller with a Kalman filter-based estimation of the real DO concentration in the bioreactor. Hsiao et al (1992) used a modified Auto-RegressiveMoving-Average model, the parameters of which were selftuned at every scan using RLS with an exponential forgetting factor. An adaptive pole placement controller was used to manipulate the aeration and agitation rates.…”

Section: Do Control Overviewmentioning

confidence: 99%

Adaptive pole placement control algorithm for DO-control in β-lactamase production

Sargantanis¹,

Karim²

1998

Biotechnol. Bioeng.

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Adaptive Control Strategy for Maintaining Dissolved Oxygen Concentration in High Density Growth of Recombinant E. coli

Cited by 27 publications

References 15 publications

Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5α)

Modified Escherichia coli B (BL21), a superior producer of plasmid DNA compared with Escherichia coli K (DH5α)

Effect of methanol feeding strategies on production and yield of recombinant mouse endostatin from Pichia pastoris

Adaptive pole placement control algorithm for DO-control in β-lactamase production

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