Comparison of polysialic acid production in Escherichia coli K1 during batch cultivation and fed-batch cultivation applying two different control strategies

Chen, Ran; John, Jinu; Rode, Bastian; Hitzmann, Bernd; Gerardy‐Schahn, Rita; Kasper, Cornelia; Scheper, Thomas

doi:10.1016/j.jbiotec.2011.04.009

Cited by 23 publications

(13 citation statements)

References 29 publications

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“…Different strategies for performing fully automated and observable processes based on soft sensor approaches have previously been investigated [4,33,34]. Mathematical modeling alone for prediction of growth and other metabolic activity of the cells is a resourceful strategy but has the drawback that the variability of the complex biological systems makes accurately predictions difficult.…”

Section: Resultsmentioning

confidence: 99%

Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein

Gustavsson

Mandenius

2012

Bioprocess Biosyst Eng

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A soft sensor approach is described for controlling metabolic overflow from mixed acid fermentation and glucose overflow metabolism in a fed-batch cultivation for production of recombinant green fluorescence protein (GFP) in Escherichia coli. The hardware part of the sensor consisted of a near-infrared in situ probe that monitored the E. coli biomass and an HPLC analyzer equipped with a filtration unit that measured the overflow metabolites. The computational part of the soft sensor used basic kinetic equations and summations for estimation of specific rates and total metabolite concentrations. Two control strategies for media feeding of the fed-batch cultivation were evaluated: (1) controlling the specific rates of overflow metabolism and mixed acid fermentation metabolites at a fixed pre-set target values, and (2) controlling the concentration of the sum of these metabolites at a set level. The results indicate that the latter strategy was more efficient for maintaining a high titer and low variability of the produced recombinant GFP protein.

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Section: Resultsmentioning

confidence: 99%

Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein

Gustavsson

Mandenius

2012

Bioprocess Biosyst Eng

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“…To control the fed‐batch cultivation, a process model based on the Monod model with limited substrate and for an ideal stirred tank bioreactor was used (Eq. ) . This differential equation system describes the cell growth in a fed‐batch stirred tank reactor.…”

Section: Methodsmentioning

confidence: 99%

“…A constant specific growth rate was adjusted during the fed‐batch phase. The program used for controlling the feeding is known as Neu‐ork (Institute for Technical Chemistry, University of Hannover), executed under MS‐DOS . The initial values for the Neu‐ork program were obtained from previous cultivations (data not shown).…”

Section: Methodsmentioning

confidence: 99%

Downstream processing of high chain length polysialic acid using membrane adsorbers and clay minerals for application in tissue engineering

Bice

Celik

Wolff

et al. 2012

Engineering in Life Sciences

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Polysialic acid (polySia) is a carbohydrate polymer of varying chain length. It is a promising scaffold material for tissue engineering. In this work, high chain length polySia was produced by an E. coli K1 strain in a 10 L bioreactor in batch-and fed-batch mode, respectively. A new downstream process for polySia is presented, based on membrane adsorber technology and use of inorganic anion exchanger. These methods enable the replacement of precipitation steps, such as acetone-, cetavlon-and ethanol-precipitation of the already established purification process. The purification process was simplified, while process efficiency and product qualities were improved. The overall yield of polySia from a 10 L batch cultivation process was 61 % and for 10 L fed-batch cultivation process 40 % with an overall purity of 98 %. The endotoxin content was determined to be negligible (14 EU mg -1 ). Th e ma i n advantage of this new downstream process is that polySia with high chain length > 130 DP (degree of polymerization) can be obtained. In fed-batch cultivation chain lengths up to 160 DP were obtained.

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“…Feed-forward control by a priori calculation of an exponential feed trajectory, based on a simple combination of mass balances and Eq. 1, has been widely exploited to maintain μ constant throughout the culture (Pico-Marco et al 2005;Ren and Yuan 2005;Babaeipour et al 2007;Jungo et al 2007;Warth et al 2010;Chenikher et al 2010;Arnau et al 2010;Chen et al 2011). The mathematical description of the exponential feed trajectory is given in Eq.…”

Section: Controlling the Specific Growth Rate In Bioprocessesmentioning

confidence: 99%

Real-time monitoring and control of microbial bioprocesses with focus on the specific growth rate: current state and perspectives

Schuler

Marison

2012

Appl Microbiol Biotechnol

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Understanding the growth characteristics of microorganisms is an essential step in bioprocessing, not only because product formation may be growth-associated but also because they might influence cell physiology and thereby product quality. The specific growth rate, a key variable of many bioprocesses, cannot be measured directly and relies on the estimation through other measurable variables such as biomass, substrate, or product concentrations. Techniques for real-time estimation of the specific growth rate in microbial fed-batch cultures are discussed in the present paper. The advantages and limitations of different models and various monitoring techniques are discussed, highlighting the importance of the specific growth rate in the development of fast, reliable, and robust processes for the production of high-value products such as recombinant proteins.

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Comparison of polysialic acid production in Escherichia coli K1 during batch cultivation and fed-batch cultivation applying two different control strategies

Cited by 23 publications

References 29 publications

Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein

Soft sensor control of metabolic fluxes in a recombinant Escherichia coli fed-batch cultivation producing green fluorescence protein

Downstream processing of high chain length polysialic acid using membrane adsorbers and clay minerals for application in tissue engineering

Real-time monitoring and control of microbial bioprocesses with focus on the specific growth rate: current state and perspectives

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