The theory of fed batch culture with reference to the penicillin fermentation

A batch culture of microbes fed continuously with culture medium is described as a “fed batch culture”. When a portion of a “fed batch culture” is withdrawn at intervals the system is described as a “repeated fed batch culture”. A fed batch culture may reach a “quasi-steady state” in which the specific growth rate (μh^?1) virtually = the dilution rate, that is, the ratio of medium flow rate to culture volume. In a quasi-steady state the specific growth rate gradually decreases. A unique feature of a fed batch culture is that it allows continuous reproduction of the transient conditions between two specific growth rates, which can be chosen at will. Fed batch culture may be used to determine the relation between specific growth rate and the growth-limiting substrate concentration and to determine the maintenance energy. Simple relations are derived to enable the concentrations of products to be predicted. The effects of different cycle times in repeated fed batch culture applied to the pencillin fermentation are discussed. Repeated fed batch culture should find a major application in the production of secondary metabolites which often are synthesised at maximum rates only transiently.     

Energetics of fungal growth: The effect of growth-limiting substrate on respiration of Penicillium chrysogenum

In sucrose-limited culture of Penicillium chrysogenum the growth yields, corrected for maintenance, for sucrose and oxygen, at dilution rates below 0.05 h^?1, were 86 g dry biomass/mol hexose and 39 g dry biomass/mol O₂. Similar yields have been observed with other moulds and with yeasts. In oxygen-limited culture the yield from oxygen was two to three times higher and the yield from sucrose about 10% higher than in sucrose-limited culture. In phosphate-limited cultures the respiration rate was unaffected by oxygen concentrations between 0.06 and 0.18 bar and by the concentration of sucrose in the medium between 0.1 M and 0.3 M. The excess of sucrose over the growth requirement was metabolised to organic acids, predominantly malate and gluconate. The results suggest that, in the presence of excess oxygen, the respiration rate is controlled by the biosynthetic demand for energy.     

Effect of ammonium chloride on plasmid DNA production in high cell density batch culture for biopharmaceutical use

In this paper the influence of ammonium salt concentration on the production of pharmaceutical grade plasmid DNA from unfed high cell density batch culture on synthetic glycerol media is presented. Ammonium chloride in different concentrations (0 mmol dm^?3, 18.7 mmol dm^?3, 37 mmol dm^?3 and 74 mmol dm^?3 supplemented) was used beside sodium glutamate as nitrogen source. Plasmid DNA concentrations of more than 50 mg dm^?3 were obtained with 37 mmol dm^?3 ammonium. The homogeneity of the DNA produced was confirmed by agarose and capillary gel electrophoresis and found to fulfil the quality requirements set for biopharmaceutical plasmid DNA with more than 90% in the supercoiled form. Copyright © 2003 Society of Chemical Industry     

Energetics of fungal growth: The effect of growth-limiting substrate on respiration of Penicillium chrysogenum

In sucrose-limited culture of Penicillium chrysogenum the growth yields, corrected for maintenance, for sucrose and oxygen, at dilution rates below 0.05 h^?1, were 86 g dry biomass/mol hexose and 39 g dry biomass/mol O₂. Similar yields have been observed with other moulds and with yeasts. In oxygen-limited culture the yield from oxygen was two to three times higher and the yield from sucrose about 10% higher than in sucrose-limited culture. In phosphate-limited cultures the respiration rate was unaffected by oxygen concentrations between 0.06 and 0.18 bar and by the concentration of sucrose in the medium between 0.1 m and 0.3 m. The excess of sucrose over the growth requirement was metabolised to organic acids, predominantly malate and gluconate. The results suggest that, in the presence of excess oxygen, the respiration rate is controlled by the biosynthetic demand for energy.     

Batch cultures of Penicillium camembertii on glucose and amino acids—model for growth and ammonium production

BACKGROUND: Three groups of amino acids were previously characterized based on their ability to be assimilated as carbon source by Penicillium camembertii. To describe the diauxic growth recorded on glucose and amino acids from the second group, such as arginine, an unstructured model was previously developed, based on the sequential consumption of both carbon substrates, glucose, followed after its exhaustion, by arginine. The model was modified to describe also the behaviour recorded during growth on other amino acids. RESULTS: The growth model involved the carbon substrate consumption (Verlhust model) and the biomass on carbon substrate yield. Glucose was therefore considered during P. camembertii growth on nitrogen source amino acids (lysine—first group); and amino acid consumption was considered during growth on carbon source amino acids (glutamate—third group), with glucose being dissimilated only for energy supply. The excess nitrogen from amino acids was released as ammonium; the linking of this production to growth was found to increase with the ability of the amino acid to be assimilated as carbon source by P. camembertii. CONCLUSION: The various metabolic behaviours recorded during P. camembertii growth on amino acids, in the presence of a primary carbon source such as glucose, were proved to be satisfactorily described by the model, showing the robustness of the model. Copyright © 2007 Society of Chemical Industry     

Effects of dissolved oxygen control on cell growth and exopolysaccharides production in batch culture ofAgaricus blazei

To investigate the effects of DOC on cell growth and EPS production, DOC was controlled at three different levels of 10, 20, and 40% of air-saturation by manipulating agitation speed in a series of batch cultures ofA. blazei. The cellular and EPS productivities increased with the DOC level up to 20%. However, DOC had no significant effects over 20%. When DOC was controlled at 20%, the cellular and EPS productivities were observed to increase 1.6-fold and 2.2-fold, respectively, as compared to the control case with no DOC control in which DOC dropped to and there-after remained at almost zero. Another batch culture was carried out with the DOC controlled at 20% by manipulating the amount of oxygen supply at a rather low agitation speed of 100 rpm. In this case, the cellular productivity was comparable to that of the former case in which DOC was controlled at the same level of 20% by manipulating agitation speed in the range of 100–450 rpm. However, the EPS productivity was about 15% lower than the former case, implying that a sufficient level of agitation is also important for EPS production.     

Equalisation of specific growth rates for syntrophic associations in batch culture

This paper describes an aspect of the growth dynamics exhibited by a ‘tight’ syntrophic association of two species in batch culture. Species X utilises substrate S and forms a product P. The substance P both inhibits the growth of X, by virtue of the thermodynamic back reaction, and constitutes the growth-limiting substrate of the organism Y. It is predicted that the resulting dynamical balance in the level of P results in an equalisation of the specific growth rates of the two populations. It is demonstrated that the equalisation of specific growth rates is a characteristic property of tight syntrophic associations in general, and occurs whenever the growth dependencies on substances S and P satisfy certain qualitative conditions.     

The metabolism of penicillium chrysogenum and the production of penicillin using a high yielding strain,at different temperatures

Results are presented for a series of penicillin V fermentations run at temperatures from 19 to 30 °C. Data are given for penicillin production, cell production and carbon dioxide evolution. Consumption of arachis oil, lactose and glucose is recorded and some additional analytical results are provided. Penicillin production reached 10 000 to 11 000 units of penicillin V/ml. Optimal temperatures were 25 to 27 °C. The results are briefly discussed, and are published in the hope that they may be of value to others working in this field.     

Mathematical model for lactic acid production from lactose in batch culture: Model development and simulation

The models available to describe lactic acid production do not seem to fit the experimental data very well, especially at the end of batch cultures. From a careful analysis of batch data, an unstructured model of the process has been derived, in which the specific growth rate variations and lactic acid concentration with time have been described by complemented logistic functions. Also, an additional term has been introduced into the Luedeking–Piret expression, taking into account the reduction in rate of lactic acid production observed at very low growth rate.     

聚氯乙烯生产的批量控制和批量管理

介绍了聚氯乙烯生产中批量控制和批量管理的概念及S88标准,提出了在聚氯乙烯生产中应用批量管理的基本方法。     

Effect of sucrose on nisin production in batch and fed‐batch culture by Lactococcus lactis

The effects of sucrose on cell growth and nisin production by Lactococcus lactis were investigated in batch and pH feed‐back controlled fed‐batch cultures. In batch cultures, nisin titer reached its maximum, 2658 IU cm^?3, at the initial sucrose concentration of 30 g dm^?3. With sucrose concentrations higher than 30 g dm^?3, nisin production decreased while the biomass was not influenced significantly. By using the pH feed‐back controlled method, residual sucrose concentration could be controlled well in fed‐batch cultures and three conditions (sucrose maintained at 2, 16, 20 g dm^?3, respectively) were evaluated. Maintaining a low sucrose concentration at 2 g dm^?3 during feeding favored nisin biosynthesis, and the maximum nisin titer obtained was 4961 IU cm^?3 compared with 3370 IU cm^?3 (16 g sucrose dm^?3)and 3498 IU cm^?3 (20 g sucrose dm^?3), respectively. Copyright © 2005 Society of Chemical Industry     

Kinetic studies in a batch reactor using ion exchange resin catalysts for oxygenates production: Role of mass transfer mechanisms

Oxygenated compounds are usually produced by a reversible liquid phase reaction using ion exchange resins with a bidisperse pore structure as catalyst. Mass transport is mainly controlled by diffusion through the macropores and the mass transfer resistance in the gel microspheres is negligible. Therefore, in this paper a mathematical model of the batch reactor considering diffusion of the species in the external film and then macropore diffusion inside the particle and reaction in the gel microspheres was developed. The numerical solution is implemented through the numerical package PDECOL and detailed explanations of the procedure used are presented. The model was applied to the diethylacetal synthesis using ethanol and acetaldehyde as reactants and Amberlyst 18 as catalyst. The experimental data are fitted with a two-parameter model based on a Langmuir-Hinshelwood rate expression in order to get the true reaction kinetics. The influence of the mass transfer mechanisms is evaluated in terms of the effectiveness factor history during the transient state of the batch reactor. The values of the effectiveness factor calculated at equilibrium with the batch reactor model are compared with those calculated from a steady state infinite bath model.     

The growth of Aspergillus terreus and the production of itaconic acid in batch and continuous cultures. The influence of pH

Aspergillus terreus (NRRL 1960) was cultivated in batch and in continuous singlestage culture. The influence of pH on the growth of the organism, on the formation of itaconic acid and on the kinetics of fermentation was studied under phosphate limitation, both at controlled pH values and also when the pH was allowed to decrease in a natural way. In the pH range 1.7–3.5, the ratio of undissociated :half-dissociated acid varied from 190:1 to 1.5:1. The amount of completely dissociated acid may be regarded as negligible. In batch systems operated without pH control, an initial pH of 3.1 proved to be the most effective. Product formation under such conditions started at a point where the exponential growth phase commenced and was described by a zero-order equation. The maximum itaconic acid production rate was shifted behind maximum growth rate. The continuous single-stage system was first order with respect to product formation. At pH > 3.1, a number of aberrant and pellet forms of the mould occurred, resulting in decreased acid production.     

Strategies of pH control and glucose‐fed batch fermentation for production of succinic acid by Actinobacillus succinogenes CGMCC1593

BACKGROUND: Succinic acid is an important precursor of numerous products, including pharmaceuticals, feed additives, green solvents, and biodegradable polymers. In this work, strategies of pH control and glucose‐fed batch fermentation for producing succinic acid using Actinobacillus succinogenes CGMCC1593 were carefully optimized. RESULTS: The production of succinic acid was stable within the pH range 6.0–7.2. Both cell growth and succinic acid production were inhibited by high concentrations of sodium and calcium ions, while there was no significant inhibition by magnesium ions. With an initial glucose concentration of 25 g L^?1, and glucose concentration was maintained between 10 and 15 g L^?1 during the course of fed batch fermentation, succinic acid concentration, productivity and yield were 60.2 g L^?1, 1.3 g L^?1 h^?1 and 75.1%, respectively. CONCLUSION: Of all the neutralization reagents used for pH control of A. succinogenes CGMCC1593, solid MgCO₃ was the most satisfactory. With increase of initial glucose concentration, the time course showed a longer growth lag period and the maximum biomass declined, while more carbon was diverted to succinate synthesis. The results obtained in this study should be helpful for the design of a highly efficient succinic acid production process. Copyright © 2008 Society of Chemical Industry     

Statistical modeling and optimization for enhanced hyaluronic acid production by batch culture of Sreptococcus zooepidemicus via the supplement of uracil

This work is aimed to achieve the optimal hyaluronic acid (HA) production by batch culture of Streptococcus zooepidemicus via the supplement of nucleotide bases using response surface methodology (RSM). First, the influence of nucleotide bases (adenine, guanine, cytosine, thymine, and uracil) on microbial HA production was investigated using fractional factorial design (FFD). By a 2⁵⁻² FFD, uracil was found to be the most significant factor for cell growth and HA production, while the other nucleotide bases were shown to have no significant effects on cell growth and HA production. Also, the impact of uracil on cell growth and HA production was further investigated by RSM, where two variables were considered: uracil concentration and supplement time. The optimal uracil concentration and supplement time were found to be 0.051g/L and 7h, respectively, and the predicted maximal HA production reached 6.42g/L. The maximal HA production increased from 5.0g/L of the control without uracil supplement to 6.31g/L at the optimal conditions in validation experiments.     

The growth and nucleation of ice in a batch Couette flow crystallizer

An experimental investigation into the crystallization characteristics of ice crystals from brine solution was carried out using a batch Couette flow crystallizer. Particle size distributions were determined by a photographic technique. The nucleation rate was correlated by the power law model: B⁰ = 26.2(P/V)^0.52 (δC^*)^1.8 μ^0.2₂ Qualitative growth characteristics were also inferred and found to be consistent with a diffusion controlling mechanism. The results obtained here suggest that early time data be emphasized in future batch crystallization experiments to more accurately determine the nucleation rate model.     

磷铵料浆浓缩加热器结垢堵塞原因及应对措施

我厂10万t/a磷酸一铵、5万t/a磷酸二铵料浆法磷铵装置,采用强制循环4效蒸发浓缩流程,完成中和料浆的浓缩。生产中料浆浓缩加热器列管结垢堵塞严重,每次检修清洗发现,少则40多根、     

Statistical modeling and optimization for enhanced hyaluronic acid production by batch culture of Sreptococcus zooepidemicus via the supplement of uracil

This work is aimed to achieve the optimal hyaluronic acid (HA) production by batch culture of Streptococcus zooepidemicus via the supplement of nucleotide bases using response surface methodology (RSM). First, the influence of nucleotide bases (adenine, guanine, cytosine, thymine, and uracil) on microbial HA production was investigated using fractional factorial design (FFD). By a 2^5-2 FFD, uracil was found to be the most significant factor for cell growth and HA production, while the other nucleotide bases were shown to have no significant effects on cell growth and HA production. Also, the impact of uracil on cell growth and HA production was further investigated by RSM, where two variables were considered: uracil concentration and supplement time. The optimal uracil concentration and supplement time were found to be 0.051 g/L and 7 h, respectively, and the predicted maximal HA production reached 6.42 g/L. The maximal HA production increased from 5.0 g/L of the control without uracil supplement to 6.31 g/L at the optimal conditions in validation experiments.     

Enhancement of biomass and pigment production during growth of Spirulina platensis in mixotrophic culture

Spirulina platensis grew mixotrophically on glucose in the light, ehancing biomass and pigment production. Under light-limited conditions, biomass production was enhanced by supplemental microbial synthesis from heterotrophic metabolism of glucose. Biomass and photosynthetic pigment production were increased 1·5–2·0-fold compared with those in autotrophic growth.