Effect of dissolved carbon dioxide on penicillin fermentations: Mycelial growth and penicillin production

Ho, Chester S.; Smith, Mark D.

doi:10.1002/bit.260280506

Cited by 45 publications

(20 citation statements)

References 6 publications

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“…Vardar and Lilly (1982) demonstrated that carbon dioxide levels in the exhaust gas of 4.2±4.8% had no impact on the speci®c penicillin production rate compared to control levels of 0.6±0.7%. A number of studies have demonstrated the inhibitory eects of carbon dioxide levels on growth, productivity, and morphology for a [Nash, 1974], Penicillium [Ho et al, 1986]). However, these studies required carbon dioxide levels greater than 5% (in the exhaust gas) before inhibitory eects were observed.…”

Section: Sensitivity To Carbon Dioxidementioning

confidence: 98%

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Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Pollard

Kirschner²,

Hernandez³

et al. 2002

Biotech & Bioengineering

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The filamentous fungus Glarea lozoyensis produces a novel, pharmaceutically important pneumocandin (B(0)) that is used to synthesize a lipopeptide which demonstrates cidal activity against clinically relevant pathogens. A range of unwanted pneumocandin analogs are also produced by the organism. To maintain the unwanted impurities to acceptable levels upon scaleup, a good understanding of the impact of chemical and physical environment on the cell physiology is required, which benefits downstream processing. Pilot-scale studies were performed to determine the impact of dissolved oxygen, temperature, pH, and carbon dioxide on the process. Experiments included multiple fermenters (up to seven) at 0.07 and 0.8 m(3) scale using single source medium sterilization and inoculum. Gas blending was used to separate effects of dissolved oxygen from agitation. The process was significantly influenced by dissolved oxygen level. The critical dissolved oxygen tension (C(crit)) for growth was below 2% air saturation. The C(crit) for production of pneumocandin B(0) was 20% air saturation, with a significant reduction of the specific production rate below this value. In contrast, low dissolved oxygen levels produced a substantial increase of pneumocandins B(1), B(5), and E(0), while high dissolved oxygen levels produced a disproportionate increase of D(5). This sensivity to dissolved oxygen was independent of agitation within a power range of 2-15 kW/m(3). Broth viscosity was impacted below 10% dissolved oxygen, suggesting an effect on morphology. The process was shown to be sensitive to temperature but relatively insensitive to pH and carbon dioxide (in the exhaust gas) within the ranges studied. This scaledown analysis explained phenomena seen at pilot scale and helped define operating boundary conditions for successful scale up to 19 m(3).

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Section: Sensitivity To Carbon Dioxidementioning

confidence: 98%

“…High levels of carbon dioxide (7± 10%) in exhaust gas have been associated with fermentations in large vessels (Onken and Liefke, 1989). These levels have shown to be detrimental to the productivity of S. erythraea (Nash, 1974), Aspergillus (McIntyre and McNeil, 1997), and Penicillium (Ho et al, 1986).…”

Section: Introductionmentioning

confidence: 97%

Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Pollard

Kirschner²,

Hernandez³

et al. 2002

Biotech & Bioengineering

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“…Two research groups have reported the effects of dissolved CO 2 in two important industrial strains, Penicillium chrysogenum (Edwards and Ho, 1988;Ho and Smith, 1986) and Aspergillus niger McNeil, 1997a,b,c, 1998). Their morphologies, being of importance in the evaluation of cell growth and product formation, were apparently affected if the influent CO 2 concentration was higher than 5%.…”

Section: Introductionmentioning

confidence: 98%

“…This would result in a CO 2 concentration in culture media much higher than with air supply only. This high CO 2 concentration may inhibit the metabolic activities of microbial cells (Ho and Smith, 1986;McIntyre and McNeil, 1997c).…”

Section: Introductionmentioning

confidence: 98%

Inhibitory effect of carbon dioxide on the fed‐batch culture of Ralstonia eutropha: Evaluation by CO₂ pulse injection and autogenous CO₂ methods

Shang

Jiang

Ryu

et al. 2003

Biotech & Bioengineering

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In order to see the effect of CO(2) inhibition resulting from the use of pure oxygen, we carried out a comparative fed-batch culture study of polyhydroxybutyric acid (PHB) production by Ralstonia eutropha using air and pure oxygen in 5-L, 30-L, and 300-L fermentors. The final PHB concentrations obtained with pure O(2) were 138.7 g/L in the 5-L fermentor and 131.3 g/L in the 30-L fermentor, which increased 2.9 and 6.2 times, respectively, as compared to those obtained with air. In the 300-L fermentor, the fed-batch culture with air yielded only 8.4 g/L PHB. However, the maximal CO(2) concentrations in the 5-L fermentor increased significantly from 4.1% (air) to 15.0% (pure O(2)), while it was only 1.6% in the 30-L fermentor with air, but reached 14.2% in the case of pure O(2). We used two different experimental methods for evaluating CO(2) inhibition: CO(2) pulse injection and autogenous CO(2) methods. A 10 or 22% (v/v) CO(2) pulse with a duration of 3 or 6 h was introduced in a pure-oxygen culture of R. eutropha to investigate how CO(2) affects the synthesis of biomass and PHB. CO(2) inhibited the cell growth and PHB synthesis significantly. The inhibitory effect became stronger with the increase of the CO(2) concentration and pulse duration. The new proposed autogenous CO(2) method makes it possible to place microbial cells under different CO(2) level environments by varying the gas flow rate. Introduction of O(2) gas at a low flow rate of 0.42 vvm resulted in an increase of CO(2) concentration to 30.2% in the exit gas. The final PHB of 97.2 g/L was obtained, which corresponded to 70% of the PHB production at 1.0 vvm O(2) flow rate. This new method measures the inhibitory effect of CO(2) produced autogenously by cells through the entire fermentation process and can avoid the overestimation of CO(2) inhibition without introducing artificial CO(2) into the fermentor.

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“…The morphology changes observed with A. pullulans may be due in part to the high concentration of dissolved carbon dioxide since a similar aggregation phenomenon has been observed with the fungus Penicillium chrysogenum when various concentrations of carbon dioxide at atmospheric pressure were bubbled through the fermentation medium (Smith and Ho 1985;Ho and Smith 1986). The anaesthetic efficiency of a molecule can be related to its olive oil/water partition coefficient (Seeman 1972).…”

Section: Methodsmentioning

confidence: 99%

The effects of pressure on the growth of Aureobasidium pullulans and the synthesis of pullulan

Dufresne

Thibault

LeDuy

et al. 1990

Appl Microbiol Biotechnol

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Effect of dissolved carbon dioxide on penicillin fermentations: Mycelial growth and penicillin production

Cited by 45 publications

References 6 publications

Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Inhibitory effect of carbon dioxide on the fed‐batch culture of Ralstonia eutropha: Evaluation by CO₂ pulse injection and autogenous CO₂ methods

The effects of pressure on the growth of Aureobasidium pullulans and the synthesis of pullulan

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Effect of dissolved carbon dioxide on penicillin fermentations: Mycelial growth and penicillin production

Cited by 45 publications

References 6 publications

Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Pilot‐scale process sensitivity studies for the scaleup of a fungal fermentation for the production of pneumocandins

Inhibitory effect of carbon dioxide on the fed‐batch culture of Ralstonia eutropha: Evaluation by CO2 pulse injection and autogenous CO2 methods

The effects of pressure on the growth of Aureobasidium pullulans and the synthesis of pullulan

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Inhibitory effect of carbon dioxide on the fed‐batch culture of Ralstonia eutropha: Evaluation by CO₂ pulse injection and autogenous CO₂ methods