On-line high-performance liquid chromatography for monitoring fermentation processes for penicillin production

Möller, J.; Hiddessen, R.; Niehoff, J.; Schügerl, K.

doi:10.1016/s0003-2670(00)82880-9

Cited by 53 publications

(8 citation statements)

References 7 publications

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“…Fermentations F1 and F2 were also fed with a solution of ammonium sulfate (10% w/v) and phenylacetic acid (PAA) (5% w/v) before inoculation to get an initial PAA concentration of 0.2 g L −1 in the fermentor, and then after 24 h at a variable flow rate, maintaining the PAA concentration between 0.5 and 1.0 g L −1 , as measured by HPLC analysis (Paul et al, 1994). This ensured that the concentration of PAA was not limiting for the penicillin G production and yet was below the toxic level of 1 g L −1 (Möller et al, 1986).…”

Section: Methodsmentioning

confidence: 99%

Effect of biomass concentration and mycelial morphology on fermentation broth rheology

Riley

Tucker

Paul

et al. 2000

Biotechnol. Bioeng.

113

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Section: Methodsmentioning

confidence: 99%

Effect of biomass concentration and mycelial morphology on fermentation broth rheology

Riley

Tucker

Paul

et al. 2000

Biotechnol. Bioeng.

113

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“…Beginning 1 h before inoculation, glucose solution (50% w/v) was added continuously at 12 mL/h. Additionally, a solution consisting of phenylacetic acid (10% w/v) and (NH 4 ) 2 SO 4 (20% w/v) was added continuously from 24 h. To keep the concentration of phenylacetic acid (PAA) below a maximum level of 1 g/L (toxic effect of PAA above 1.5 g/L; Möller et al, 1986), the flow rate was adjusted manually (between 2-5 mL/h) using HPLC data (see below) to monitor the PAA concentration. Each fermentation was inoculated with a vegetative inoculum grown in a 2 L shake flask (1 L working volume) for 36 h on the complex medium of Queener and Swartz (1979).…”

Section: Fed-batch Fermentationsmentioning

confidence: 99%

Dependence ofPenicillium chrysogenum growth, morphology, vacuolation, and productivity in fed-batch fermentations on impeller type and agitation intensity

Jüsten

Paul

Nienow

et al. 1998

Biotechnol. Bioeng.

103

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The influence of the agitation conditions on the growth, morphology, vacuolation, and productivity of Penicillium chrysogenum has been examined in 6 L fed‐batch fermentations. A standard Rushton turbine, a four‐bladed paddle, and a six‐bladed pitched blade impeller were compared. Power inputs per unit volume of liquid, P/VL, ranged from 0.35 to 7.4 kW/m3. The same fermentation protocol was used in each fermentation, including holding the dissolved oxygen concentration above 40% air saturation by gas blending. The mean projected area (for all dispersed types, including clumps) and the clump roughness were used to characterize the morphology. Consideration of clumps was vital as these were the predominant morphological form. For a given impeller, the batch‐phase specific growth rates and the overall biomass concentrations increased with agitation intensity. Higher fragmentation at higher speeds was assumed to have promoted growth through increased formation of new growing tips. The mean projected area increased during the rapid growth phase followed by a sharp decrease to a relatively constant value dependent on the agitation conditions. The higher the speed, the lower the projected area for a given impeller type. The proportion by volume of hyphal vacuoles and empty regions decreased with speed, possibly due to fragmentation in the vacuolated regions. The specific penicillin production rate was generally higher with lower impeller speed for a given impeller type. The highest value of penicillin production as well as its rate was obtained using the Rushton turbine impeller at the lowest speed. At given P/VL, changes in morphology, specific growth rate, and specific penicillin production rate depended on impeller geometry. The morphological data could be correlated with either tip speed or the “energy dissipation/circulation function,” but a reasonable correlation of the specific growth rate and specific production rate was only possible with the latter. © 1998 John Wiley & Sons, Inc. Biotechnol Bioeng 59:762–775, 1998.

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“…Key advantages of sample removal were that some interfering substances were removed from broth via sample pretreatment and sterilization of the sensor itself was avoided (Lüdi et al, 1992), permitting use of biosensors which previously had limited in situ application due to their heat sensitivity (Schügerl, 2001). These sampling systems were either located externally to the fermenter or more recently utilized steam-sterilizable filtration probes situated inside the fermenter containing micro/ultra-filtration membranes (e.g., polysulfone, polycarbonate, hydrophilized polypropylene) of appropriate molecular weight cut-offs to avoid particle introduction into the analyzer (Chase, 1986;Möller et al, 1986;Niehoff et al, 1986;Rank et al, 1992) or automated centrifugation (Turner et al, 1993(Turner et al, , 1994. When cell broth was sampled for intracellular enzyme activity measurements, a reliable and automated method of cell wall permeabilization (Ahlmann et al, 1986;Blankenstein and Kula, 1991) or cell wall disintegration (Steube and Spohn, 1994) was required.…”

Section: Current Pat In Bioprocessing (During Thementioning

confidence: 99%

“…Penicillin and its by-products/precursors Penicillium chrysogenum Continuous measurement in complex medium to determine optimal harvest time since product degrades Möller et al (1986) Cephalosporin and its by-products…”

Section: Streptomcyes Erythreusmentioning

confidence: 99%

Bioprocess monitoring and computer control: Key roots of the current PAT initiative

Junker

Wang

2006

Biotech & Bioengineering

113

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This review article has been written for the journal, Biotechnology and Bioengineering, to commemorate the 70th birthday of Daniel I.C. Wang, who served as doctoral thesis advisor to each of the co-authors, but a decade apart. Key roots of the current PAT initiative in bioprocess monitoring and control are described, focusing on the impact of Danny Wang's research as a professor at MIT. The history of computer control and monitoring in biochemical processing has been used to identify the areas that have already benefited and those that are most likely to benefit in the future from PAT applications. Past applications have included the use of indirect estimation methods for cell density, expansion of on-line/at-line and on-line/in situ measurement techniques, and development of models and expert systems for control and optimization. Future applications are likely to encompass additional novel measurement technologies, measurements for multi-scale and disposable bioreactors, real time batch release, and more efficient data utilization to achieve process validation and continuous improvement goals. Dan Wang's substantial contributions in this arena have been one key factor in steering the PAT initiative towards realistic and attainable industrial applications.

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On-line high-performance liquid chromatography for monitoring fermentation processes for penicillin production

Cited by 53 publications

References 7 publications

Effect of biomass concentration and mycelial morphology on fermentation broth rheology

Effect of biomass concentration and mycelial morphology on fermentation broth rheology

Dependence ofPenicillium chrysogenum growth, morphology, vacuolation, and productivity in fed-batch fermentations on impeller type and agitation intensity

Bioprocess monitoring and computer control: Key roots of the current PAT initiative

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