Effect of conditions of agitation and aeration on the biosynthesis of oleandomycin

The data on the effect of the aeration and agitation conditions on biosynthesis of oleandomycin in 0.75, 3 and 50 m3 apparatus are presented. The relationship between the biosynthetic parameters, oxygen dissolution rate and specific power consumption for agitation was studied. It was shown that the values of the specific power consumption for agitation were not acceptable for scaling up the process of oleandomycin biosynthesis.     

Optimum autoregulator addition strategy for maximum virginiamycin production in batch culture of Streptomyces virginiae

Virginiae butanolides (VBs) are autoregulators of Streptomyces virginiae, which induce virginiamycin biosynthesis. Generally, autoregulators are synthesized by the microorganism itself during culture. Addition of chemically synthesized virginiae butanolide-C (VB-C), which is one of the VBs, can also control the induction time and the amount of virginiamycin production. The optimum concentration and shot-feeding time of VB-C for the maximum production of virginiamycins M and S were investigated in flasks and jar-fermentor batch cultures. VB-C addition later than 8 h from the start of culture induced not only virginiamycin M and S synthesis but also VB synthesis. Virginiamycin M and S production increased with the decrease of total VBs (produced VBs and added VB-C) concentration. That is, although VBs are needed to induce virginiamycin M and S synthesis, the amount of VB-C added should be such that as small an amount as possible of VBs is synthesized to achieve the maximum production of virginiamycins M and S. However, the VB-C addition earlier than 8 h from the start of culture showed no clear relationship between the amounts of VBs and virginiamycins M and S produced. In conclusion, the maximum production of virginiamycins M and S was attained by the shot addition of 5 mug/L VB-C at 8 h from the start of culture. The maximum value was about twofold that without VB-C addition. The optimum addition strategy of VB-C was confirmed by the jar-fermentor experiments. (c) 1995 John Wiley & Sons, Inc.     

Optimization of the aeration and agitation speed of Aeribacillus palidus 418 exopolysaccharide production and the emulsifying properties of the product

The specific properties of exopolysaccharides (EPS) from thermophilic microorganisms have attracted interest in their optimized production. In this study, the ability of Aeribacillus pallidus 418 to grow and produce polysaccharide in a 5-l stirred tank bioreactor was investigated. Agitation rates of 100, 200, 600, 900, and 1100 revolutions per minute (rpm), at an air flow rate of 0.5 gas volumes per unit medium volume per minute (vvm), and aeration rates of 0.25, 0.5, 1.0, and 1.5 vvm, at an agitation rate of 900 rpm, were examined. A maximum EPS yield of 170 μg/ml has been registered in a single impeller bioreactor equipped with an original Narcissus impeller at agitation speed of 900 rpm, with an aeration rate of 0.5 vvm. The bioprocess oxygen uptake rate (OUR) and oxygen mass transfer coefficient (K_La) were evaluated. The emulsifying properties of the specific EPS produced by A. pallidus 418 were determined. Stable oil-in-water emulsions, a low level of separated water phase and high dispersion stability were found, which together demonstrate the prospects for the industrial exploration of EPS production. Enhanced synergism between the A. pallidus 418 synthesized EPS and various commercially used hydrocolloids was observed; superior synergy was achieved in combination with xanthan gum.     

Effect of aeration and agitation on yeast inulinase production: a biocalorimetric investigation

Bioprocess and Biosystems Engineering - Air flow rate and agitation speed for inulinase production by Kluyveromyces marxianus were optimized based on metabolic heat release profiles. Shear stress...     

Effect of pH,agitation and aeration on hyaluronic acid production byStreptococcus zooepidemicus

Summary The optimum pH for both the rate of production and yield of hyaluronic acid (HA) byStreptococcus zooepidemicus from glucose medium was 6.7±0.2 under anaerobic conditions. High agitation rates (600 rpm) gave superior results compared to 300 rpm. Aeration of the culture (0.3 VVM) improved the HA yield, but not the rate of production and lead to some acetate and CO₂ being formed, in addition to lactate and HA.     

Optimisation of agitation and aeration in fermenters

The problem of optimising agitation and aeration in a given fermenter is addressed. The objective function is total electric power consumed for agitation, compression and refrigeration. The major constraint considered is to ensure that the dissolved oxygen concentration is above the critical value. It is shown that it is possible to analytically calculate the optimal pair (air flowrate, stirrer speed) and that, at least for the industrial antibiotics fermentation used as case-study, the optimum lies within a window for satisfactory operation, limited by other possible constraints to the problem. Savings achievable by optimal operation as compared with current industrial procedure were found to be around 10% at pilot plant scale (0.26 m³) and 20% at full scale (85 m³).List of Symbols A fermenter cross sectional area (m²) - C dissolved oxygen concentration (mole m^–3) - C ^* DO concentration in equilibrium with the gas (mole m^–3) - C _crit critical DO concentration (mole m^–3) - C _p specific heat of air at constant pressure (J kg^–1 K^–1) - C _sp dissolved oxygen set point (mole m^–3) - C _v specific heat of air at constant volume (J kg^–1 K^–1) - D agitator diameter (m) - f pressure correction of air flow-rate - (Fl _g)_F aeration number at flooding - (Fr _g)_F froude number at flooding - k coefficient in expression for mass transfer coefficient - K _La volumetric oxygen transfer coefficient (s^–1) - m power exponent in expression for mass transfer coefficient - n gas flow rate exponent in expression for mass transfer coefficient - n ^* number of impellers - N rotation speed (s^–1) - N _F rotation speed at flooding (s^–1) - N _p unaerated power number - N _pg aerated power number - OUR Oxygen Uptake Rate (mole m^–3 s^–1) - p ₀ atmospheric pressure (N m^–2) - p ₁ compressor exit pressure (N m^–2) - p ₂ pressure at the bottom of the fermenter (N m^–2) - p ₃ pressure at the top of the fermenter (N m^–2) - P _c compression power (W) - P _d power added by expansion (W) - P _ev power removed by evaporation (W) - P _g agitation power (W) - P _m power added by metabolism (W) - P _r power removed by refrigeration (W) - P _t total power (W) - Q air flow-rate at atmospheric conditions (m³ s^–1) - Q _f air flow-rate at average fermenter conditions (m³ s^–1) - s ₀ absolute humidity at atmospheric conditions - s ₃ absolute humidity at fermenter exit - T tank diameter (m) - V liquid volume (m³) - v _s gas superficial velocity (m s^–1) - _i parameter defined in the text - safety margin for dissolved oxygen (mole m^–3) - ratio of specific heats of air - _g agitation efficiency - _c compression efficiency - _r refrigeration efficiency - liquid density (kg m^–3) - _g air density (kg m^–3) - latent heat of vaporisation of water (J kg^–1) The authors are grateful to Elsa Silva, Carlos Lopes, Carlos Aguiar, Fernando Mendes, and Alexandre Cardoso, who helped with parts of this work, and to CIPAN for permission to publish these data.     

Effect of the aeration and agitation parameters on the oxytetracycline biosynthesis process under microkinetic conditions

The effect of the aeration levels in flasks on the rate of oxytetracycline biosynthesis and other kinetic characteristics was studied. It was shown that changes in the medium volume in flasks, dilution of the fermentation broth with water or its filtrate and the use of oxygen for aeration had a significant effect on the characteristics studied. Special experiments with low concentrations of the biomass were performed for investigation of the effect of dissolved carbon dioxide on the kinetics of the process.     

The role of aeration and agitation in the production of glucose oxidase in submerged culture

The influence of agitation and aeration on growth and on production of glucose oxidase of Asp. niger has been studied. It was found that both rate of growth and glucose oxidase production was higher at an agitation speed of 700 rpm than at 460 rpm. Further increase in speed of agitation resulted in neither a higher rate of growth nor a higher glucose oxidase activity. Total glucose oxidase activity was highest in a medium containing 5% sugar (at an agitation speed of 700 rpm) and did not get higher when the sugar concentration of the medium was increased to 7%. When pure oxygen was bubbled through the culture the rate of growth of the culture (in the linear phase) was 95 mg. mycelial dry wt./100 ml./hr., and only 61 mg. when air was applied. The glucose oxidase activity of oxygenated culture was double the activity of aerated culture. Viscosity of the homogenized culture became higher with higher concentration of mycelia. The viscosity of oxygenated culture was found to be lower than that of aerated culture.     

The effect of aeration and agitation on tetracycline biosynthesis

The results of the study on relation between tetracycline biosynthesis and the specific power input for agitation in pilot plant apparatus was studied. No correlation was observed between the levels of tetracycline biosynthesis and changes in the specific power input within a range of 0.6 to 2.3 kW/m3 at the expense of changes in the mixer diameter and the agitation rate, when the aeration rate was constant. It was shown that the aeration conditions were most significant for tetracycline biosynthesis. The study provided determination of the optimal aeration conditions for biosynthesis of tetracycline.     

Effect of agitation and aeration on the citric acid production by Yarrowia lipolytica grown on glycerol

The effects of agitation rates from 400 to 900 rpm and aeration rates ranging from 0.18 to 0.6 vvm on biomass and citric acid production on glycerol media by acetate-negative mutants of Yarrowia lipolytica, Wratislavia 1.31 and Wratislavia AWG7, in batch culture were studied. The agitation rates of 800 and 900 rpm (at a constant aeration rate of 0.36 vvm) and aeration rates within the range of 0.24-0.48 vvm (at a constant agitation rate of 800 rpm), which generated dissolved oxygen concentration (DO) higher than 40%, were found the best for citric acid biosynthesis from glycerol. An increase in agitation rate (higher than 800 rpm) and aeration rate (higher than 0.36 vvm) had no impact on DO and citric acid production. The highest citric acid concentration (92.8 g/L) and yield (0.63 g/g) were obtained with Wratislavia 1.31 strain at 0.24 vvm. The highest volumetric citric acid production rate (1.15 g/Lh) and specific citric acid production rate (0.071 g/gh) were reached at 0.48 vvm.     

Effects of agitation and aeration on the production of extracellular glucose oxidase from a recombinant Saccharomycescerevisiae

A recombinant strain of Saccharomyces cerevisiae, GAL-GO2, was developed to facilitate the production of extracellular glucose oxidase (GOD). The recombinant strain secreted 85% (8.7?U/ml) of the total GOD (10.3?U/ml) produced in shake flask culture. For further enhancement of GOD production, optimization of the speed of agitation and the rate of aeration in a stirred tank fermentor was carried out. Response surface methodology with appropriate statistical experimental design was employed for this purpose. The maximal level of extracellular GOD was achieved when the speed of agitation and the rate of aeration were 420?rpm and 0.25?vvm, respectively. The enzyme production was increased by 74% compared to the level obtained under unoptimized conditions.     

Optimization of fermentation conditions for alcohol production

The quantitative effects of carbohydrate levels, degree of initial saccharification, glucoamylase dosage, temperature, and fermentation time were investigated using a Box-Wilson central composite design protocol. With Saccharomyces cerevisiae ATCC 4126, it was found that the use of a partially saccharified starch substrate markedly increased yields and attainable alcohol levels. Balancing the degree of initial saccharification with the level of glucoamylase used to complete hydrolysis was found necessary to obtain optimum yields. The temperature optimum was found to be 36 degrees C. The regression equations obtained were used to model the fermentation in order to determine optimum fermentation conditions.     

The role of aeration and agitation in the production of glucose oxidase in submerged culture. II

The main purpose of the work reported here was to establish the effectiveness of aeration and agitation, and to determine the best conditions of aeration for the growth and production of glucose oxidase of Aspergillus niger, on a semi-industrial scale. Concentration of dissolved O₂, O₂ consumption and CO₂ production were measured. It was found that the rate of growth and the activity of glucose oxidase per gram mycelium increased with the increase of speed of agitation. The concentration of dissolved oxygen of the fermentation broth, as well as the rate of respiration (O₂ consumption and CO₂ production) increased in direct proportion to the increase of speed of agitation, while assimilation of sugars was accelerated. The values of the respiratory ratio showed a fluctuation according to the presence or absence of sugar in the medium.     

Butanediol production by Aerobacter aerogenes NRRL B199: effects of initial substrate concentration and aeration agitation

Butanediol production by Aerobacter aerogenes NRRL B199 grown on glucose requires an optimal rate of aeration for the obtention of butanediol 2, 3. In the absence of air, Aerobacter aerogenes NRRL B199 growth and production are weak. Agitation-aeration is necessary for producing the biomass, but an excess of oxygen proves to be toxic with regard to metabolite production. Oxygen is a limiting substrate with regard to growth and an inhibitor with regard to the specific metabolite productivity. This observation is discussed from a kinetic stand point and in relation to the search for the optimum oxygen transfer coefficient (K(L)a), which is found to be in the range of 50-100h(-1). It has also been observed that K(L)a increases during the fermentation cycle. The initial substrate concentration effects the yield production of biomass and butanediol production. Low yields of butanediol are obtained at low initial sugar concentrations, but good yields of butanediol are obtained (0.45 g/g) at high concentrations of glucose (195 g/L). Carbon substrates and butanediol are inhibitors of cell growth while butanediol is not quite an inhibitor of the specific rate of butanediol production for the range of butanediol of 0-100 g/L.     

星形孢菌素的发酵条件优化

提高抗生素在产生菌中的表达效价,从而降低生产成本,是实现抗生素生产应用的重要基础.星形孢菌素是一种非特异性的蛋白激酶抑制剂,能够诱导多种类型的细胞凋亡,但目前星形孢菌素生产菌株的表达效价均较低,达不到生产要求,使其应用受到限制[1-4].     

Maximum virginiamycin production by optimization of cultivation conditions in batch culture with autoregulator addition

A strategy for optimization of non-growth-associated production in batch culture employing an empirical approach was developed through the study of virginiamycin production. The strategy is formulated with two aims: attaining a high cell concentration at the beginning of the production phase without decrease in production activity; and enhancing the production activity during the production phase. As a practical example, the goal of a maximum virginiamycin (M and S) production in the batch culture of Streptomyces virginiae was set. To attain a high cell concentration in the production phase of the batch culture, that is, to extend the growth phase for as long as possible, the optimum composition and concentration of the complex medium, especially the yeast extract (YE) concentration, were first investigated. Dissolved oxygen (DO) concentration control was also a parameter considered in maintaining the production activity during the production phase. In addition, to enhance the production activity, an optimum addition strategy of an autoregulator, virginiae butanolide-C (VB-C), was investigated. Combining these measures, the optimum cultivation conditions were found to be an initial YE concentration in the complex medium of 45 g/L, the shot addition of 300 mug/L of VB-C 11.5 h after the start of the batch culture, and a DO concentration maintained above 2 mg/L. The maximum concentrations of virginiamycin M and S were about ninefold those obtained under nonoptimum cultivation conditions. Nonoptimum cultivation conditions consisted of an initial YE concentration one sixth (7.5 g/L) that of the optimum cultivation conditions, and no VB-C addition. These conditions were used as representative of the standard cultivation of virginiamycin in this study. The strategy developed here will be applicable to the production of other antibiotics, especially to the cultivation of Streptomyces species, in which a hormonelike signal material (an autoregulator) plays an important role in antibiotic production. (c) 1996 John Wiley & Sons, Inc.