Correlation for the maximum oxygen transfer capacity in shake flasks for a wide range of operating conditions and for different culture media

Meier, Klaus; Klöckner, Wolf; Bonhage, Benjamin; Antonov, Elena; Regestein, Lars

doi:10.1016/j.bej.2016.01.014

Cited by 74 publications

(89 citation statements)

References 55 publications

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“…Shaking flask cultivations of A. namibiensis using either the non-supplemented medium 5294 or one of two salt supplements did not show any plateauing of the OTR at high values ( Figure 5A). Additionally, none of the cultures reached OTR values close to the theoretical maximum oxygen transfer capacity of 9.3 mmol L −1 h −1 (according to Meier et al [61] at an osmolality of 0.48 osmol kg −1 , see Supporting Information Figure S2). Therefore, an oxygen limitation caused by the process conditions can be ruled out.…”

Section: Increase In Productivity By Salt-enhanced Cultivationsupporting

confidence: 52%

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Salt‐enhanced cultivation as a morphology engineering tool for filamentous actinomycetes: Increased production of labyrinthopeptin A1 in Actinomadura namibiensis

Tesche

Rösemeier-Scheumann

Lohr

et al. 2019

Engineering in Life Sciences

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Salt‐enhanced cultivation as a morphology engineering tool for the filamentous actinomycete Actinomadura namibiensis was evaluated in 500‐mL shaking flasks (working volume 100 mL) with the aim of increasing the concentration of the pharmaceutically interesting peptide labyrinthopeptin A1. Among the inorganic salts added to a complex production medium, the addition of (NH4)2SO4 led to the highest amount of labyrinthopeptin A1 production. By using 50 mM (NH4)2SO4, the labyrinthopeptin A1 concentration increased up to sevenfold compared to the non‐supplemented control, resulting in 325 mg L−1 labyrinthopeptin A1 after 10 days of cultivation. The performance of other ammonium‐ and sulfate‐containing salts (e.g., NH4Cl, K2SO4) was much lower than the performance of (NH4)2SO4. A positive correlation between the uptake of glycerol as one of the main carbon sources and nongrowth‐associated labyrinthopeptin productivity was found. The change in the cell morphology of A. namibiensis in conjunction with increased osmolality by the addition of 50 mM (NH4)2SO4, was quantified by image analysis. A. namibiensis always developed a heterogeneous morphology with pellets and loose mycelia present simultaneously. In contrast to the non‐supplemented control, the morphology of (NH4)2SO4‐supplemented cultures was characterized by smaller and circular pellets that were more stable against disintegration in the stationary production phase.

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Section: Increase In Productivity By Salt-enhanced Cultivationsupporting

confidence: 52%

“…Additionally, none of the cultures reached OTR values close to the theoretical maximum oxygen transfer capacity of 9.3 mmol L −1 h −1 (according to Meier et al. at an osmolality of 0.48 osmol kg −1 , see Supporting Information Figure S2). Therefore, an oxygen limitation caused by the process conditions can be ruled out.…”

Section: Resultsmentioning

confidence: 99%

Salt‐enhanced cultivation as a morphology engineering tool for filamentous actinomycetes: Increased production of labyrinthopeptin A1 in Actinomadura namibiensis

Tesche

Rösemeier-Scheumann

Lohr

et al. 2019

Engineering in Life Sciences

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“…Throughout phases II and III, more or less constant k L a values of 215 ± 11 hr −1 were obtained. These values are in good agreement with an empirical correlation (200 ± 27 hr −1 ) found in the literature for nonviscous culture broths (Meier et al, ).…”

Section: Resultssupporting

confidence: 91%

“…This can be attributed to the slightly increased viscosity during phase II (~3.5 mPa s) and is in agreement with the findings of Giese et al (). According to the empirical correlation presented by Meier et al (), k L a values of 339 ± 27 hr −1 are expected at water‐like viscosities for the applied synthetic V3 medium. This is in the same order of magnitude as the calculated values at the beginning of exponential growth (13 hr).…”

Section: Resultsmentioning

confidence: 82%

Combined dissolved oxygen tension and online viscosity measurements in shake flask cultivations via infrared fluorescent oxygen‐sensitive nanoparticles

Ladner

Flitsch

Lukacs

et al. 2019

Biotech & Bioengineering

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Oxygen supply is one of the most critical process parameters in aerobic cultivations.To assure sufficient oxygen supply, shake flasks are usually used in combination with orbital shaking machines. In this study, a measurement technique for the dissolved oxygen tension (DOT) in shake flask cultures with viscosity changes is presented. The movement of the shaker table is monitored by means of a Hall effect sensor. For DOT measurements, infrared fluorescent oxygen-sensitive nanoparticles are added to the culture broth. The position of the rotating bulk liquid needs to be determined to assure measurements inside the liquid. The leading edge of the bulk liquid is detected based on the fluorescence signal intensity of the oxygen-sensitive nanoparticles. Furthermore, online information about the viscosity of the culture broth is acquired due to the detection of the position of the leading edge of the bulk liquid relative to the direction of the centrifugal force, as described by Sieben et al. (2019. Sci. Rep., 9, 8335). The DOT measurement is combined with a respiration activity monitoring system which allows for the determination of the oxygen transfer rate (OTR) in eight parallel shake flasks. Based on DOT and OTR, the volumetric oxygen transfer coefficient (k L a) is calculated during cultivation. The new system was successfully applied in cultivations of Escherichia coli, Bacillus licheniformis, and Xanthomonas campestris. K E Y W O R D S dissolved oxygen tension, optical measurement, oxygen-sensitive nanoparticles, RAMOS, shake flask, viscosity

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“…The different performance in the two cultivation settings might be explained by differences in the oxygen transfer rate, which according to Meier et al. is much lower in SFs at the set frequency of 90 rpm, potentially too low to sustain optimal ATP formation and succinate production . A more in‐depth study of the dependence of succinate synthesis on oxygen availability might be valuable to improve production further.…”

Section: Resultsmentioning

confidence: 97%

Evaluation of pyruvate decarboxylase‐negative Saccharomyces cerevisiae strains for the production of succinic acid

Ahmed

Küttner

Blank

et al. 2019

Engineering in Life Sciences

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Dicarboxylic acids are important bio‐based building blocks, and Saccharomyces cerevisiae is postulated to be an advantageous host for their fermentative production. Here, we engineered a pyruvate decarboxylase‐negative S. cerevisiae strain for succinic acid production to exploit its promising properties, that is, lack of ethanol production and accumulation of the precursor pyruvate. The metabolic engineering steps included genomic integration of a biosynthesis pathway based on the reductive branch of the tricarboxylic acid cycle and a dicarboxylic acid transporter. Further modifications were the combined deletion of GPD1 and FUM1 and multi‐copy integration of the native PYC2 gene, encoding a pyruvate carboxylase required to drain pyruvate into the synthesis pathway. The effect of increased redox cofactor supply was tested by modulating oxygen limitation and supplementing formate. The physiologic analysis of the differently engineered strains focused on elucidating metabolic bottlenecks. The data not only highlight the importance of a balanced activity of pathway enzymes and selective export systems but also shows the importance to find an optimal trade‐off between redox cofactor supply and energy availability in the form of ATP.

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Correlation for the maximum oxygen transfer capacity in shake flasks for a wide range of operating conditions and for different culture media

Cited by 74 publications

References 55 publications

Salt‐enhanced cultivation as a morphology engineering tool for filamentous actinomycetes: Increased production of labyrinthopeptin A1 in Actinomadura namibiensis

Salt‐enhanced cultivation as a morphology engineering tool for filamentous actinomycetes: Increased production of labyrinthopeptin A1 in Actinomadura namibiensis

Combined dissolved oxygen tension and online viscosity measurements in shake flask cultivations via infrared fluorescent oxygen‐sensitive nanoparticles

Evaluation of pyruvate decarboxylase‐negative Saccharomyces cerevisiae strains for the production of succinic acid

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