Adaptive on‐line model for aerobic <i>Saccharomyces cerevisiae</i> fermentation

Schalien, Randolf von; Fagervik, Kaj; Saxén, Bjørn; Ringbom, Knut; Rydström, Mikael

doi:10.1002/bit.260480611

Cited by 20 publications

(7 citation statements)

References 8 publications

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“…Such methods are often only applicable for repetitive processes. Further methods require a numerical solution of differential equations (von Schalien et al, 1995), leading to a lack in robustness because of measurement noise and a lack of consistency testing of the acquired data. A new approach for setting up material balances of cultures during metabolic transitions has recently been initiated (Duboc and von Stockar, 1995), but their approach used off-line sampling only.…”

Section: Introductionmentioning

confidence: 99%

On‐line stoichiometry and identification of metabolic state under dynamic process conditions

Herwig

Marison

Stockar

2001

Biotech & Bioengineering

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A method for the on-line calculation of conversion rates and yield coefficients under dynamic process conditions was developed. The method is based on cumulated mass balances using a moving average method. Elemental balances were used to test the measured cumulated quantities for gross errors and inappropriate stoichiometry definition followed by data reconciliation and estimation of non-measured conversion rates, using a bioprocess set-up including multiple on-line analysis techniques. The quantitative potential of the proposed method is demonstrated by executing transient experiments in aerobic cultures of Saccharomyces cerevisiae on glucose. Rates and yield coefficients could be consistently quantified in shift-up, shift-down, and accelerostat experiments. The method shows the capability to describe quantitatively transient changes in metabolism including uncoupling of catabolism and anabolism, also for the case when multiple components of metabolism are not measured. The validity of the experiment can be evaluated on-line. Additionally, the method detects with high sensitivity inappropriate stoichiometry definition, such as a change in state of metabolism. It was shown that concentration values can be misleading for the identification of the metabolic state. In contrast, the proposed method provides a clear picture of the metabolic state and new physiological regulations could be revealed. Hence, the novelty of the proposed method is the on-line availability of consistent stoichiometric coefficients allowing a significant speed up in strain characterization and bioprocess development using minimal knowledge of the metabolism. Additionally, it opens up the use of transient experiments for physiological studies.

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Section: Introductionmentioning

confidence: 99%

On‐line stoichiometry and identification of metabolic state under dynamic process conditions

Herwig

Marison

Stockar

2001

Biotech & Bioengineering

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“…Other important variables such as biomass and substrate concentration must be measured off-line with a significant time delay. However, these parameters can be estimated from on-line measurable variables such as carbon dioxide evolution rate (CER), oxygen uptake rate (OUR), and respiratory quotient (RQ) (Chattaway et al, 1992;Heinzle and Reuss, 1987;Von Schalien et al, 1995).…”

Section: Introductionmentioning

confidence: 99%

Enhancement of Candida rugosa lipase production by using different control fed‐batch operational strategies

Gordillo¹,

Sanz²,

Sánchez³

et al. 1998

Biotechnol. Bioeng.

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Simulation studies have predicted that maximum lipase activity is reached with fed-batch operation strategies. In this work, two different fed-batch operational strategies have been studied: constant substrate feeding rate and specific growth rate control. A constant substrate feeding rate strategy showed that maximum aqueous lipolytic activity (55 U/mL) was reached at low substrate feeding rates, whereas lipase tends to accumulate inside the cell at higher rates of substrate addition. In the second fed-batch strategy studied, a feedback control strategy has been developed based on the estimation of state variables (X and mu) from the measurement of indirect variables such as CER by means of mass spectrometry techniques. An on-off controller was then used to maintain the specific growth rate at the desired value by adjusting the substrate feeding rate. A constant specific growth rate strategy gave higher final levels of aqueous lipolytic activity (117 U/mL) at low specific growth rates. At higher specific growth rates the enzyme remained accumulated inside the cell, as was observed with a constant feeding fed-batch strategy. With a constant specific growth rate strategy, lipase production by Candida rugosa was enhanced 10-fold compared to a batch operation. Purification studies have demonstrated that lipolytic and esterasic specific activity ratios of Candida rugosa isoenzymes can be modified by using different operational conditions. These studies have also showed that the isoenzymes obtained in a controlled growth rate strategy are around three- to four-fold more active than those obtained in a constant feeding rate strategy.

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“…At the same time, the feed started and the glucose concentration was kept at 40 g l A1 until a total of 208 g had been consumed. The control was based on glucose estimates from an adaptive on-line simulation model, described in von Schalien et al [16] and Fagervik et al [17] None of the fed-batch strategies led to better results than those which were obtained with a batch run.…”

Section: Resultsmentioning

confidence: 99%

Optimization of an Aspergillus niger glucose oxidase production process

Rothberg

Weegar

Schalien

et al. 1999

Bioprocess Engineering

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The purpose of the present study was to ascertain the optimal concentration of dissolved oxygen in order to maximize the intracellular glucose oxidase formation in Aspergillus niger. Cultivations performed in a 3.5 l laboratory reactor showed that a dissolved oxygen concentration at 3% of saturation at a total pressure of 1.2 bar was optimal for maximizing intracellular glucose oxidase activity. Cultivations performed at higher dissolved oxygen concentrations did not produce as much glucose oxidase as those performed at 3%, although the formation rate was high. Experiments revealed that maximal intracellular glucose oxidase formation for the A. niger strain used, is accomplished by limiting the gluconic acid production rate by means of maintaining a low dissolved oxygen concentration. Several attempts to achieve higher intracellular glucose oxidase activity were also made by manipulating the glucose concentration at a 3% dissolved oxygen concentration. However, no enhancement in glucose oxidase activity was observed.

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Adaptive on‐line model for aerobic Saccharomyces cerevisiae fermentation

Cited by 20 publications

References 8 publications

On‐line stoichiometry and identification of metabolic state under dynamic process conditions

On‐line stoichiometry and identification of metabolic state under dynamic process conditions

Enhancement of Candida rugosa lipase production by using different control fed‐batch operational strategies

Optimization of an Aspergillus niger glucose oxidase production process

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