摘要:

AbstractTwo basic questions in bioprocess modeling are how many rate equations must be specified and which processes (substrate uptake, product formation, etc.) they should describe. The number of rate equations is constrained by the yield equations, which represent the balances of reducing power, energy in the form of ATP, and the various elements involved in microbial metabolism. These balances are derived from a simplified picture that divides metabolism into catabolic, anabolic, respiratory, and product formation pathways. The linear growth equation for aerobic metabolism and the Ludeking–Piret equation for product formation by fermentation are derived from these balances, and the yield coefficients are related to the metabolic parameters, YATP(P/O), etc. The use of oxygen for purposes other than respiration is included in the analysis and extends the idea of a constant “yield on available electrons” to very reduced substrates. These balances specify the number of degrees of freedom, i.e., the number of pieces of information required to complete the description of the system. This information may be in the form of measurements, knowledge of the biochemical pathways, or rate equations. The number of rate measurements available (usually two, the consumption rates of O2and CO2) versus the number needed defines the state estimation problem in bioprocess control. Rate equations usually specify the biomass growth rate, but it may be preferable to specify the specific consumption rate of the limiting nutrient. © 1993 John Wiley&Son

ISSN:0006-3592    

DOI:10.1002/bit.260420502

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA simple mathematical model is developed to help explain the complex population dynamics of an Escherichia coli host–plasmid expression/excretion system for β‐lactamase within single‐ and two‐stage reactors. The model successfully integrates the individual regulatory (tac promoter induction), genetic (runaway plasmid replication), and population dynamics (culture instability) aspects of the system. The model predicts, and experiment confirms, that high‐level β‐lactamase production and excretion cannot be easily maintained in single‐stage reactors using the current plasmid construction. Stable target protein production and excretion is mathematically predicted, and experimentally confirmed, within two‐stage reactors. The model is used to provide insight into engineering a more stable host–vector expression/excretion system for use in single‐stage reactors. © 199

ISSN:0006-3592    

DOI:10.1002/bit.260420503

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractA new technique based on a fractal model has been developed for the quantification of the macroscopic morophology of mycelia. The morphological structuring is treated as a fractal object, and the fractal dimension, determined by an ultrasonic scattering procedure developed for the purpose, serves as a quantitative morphological index. Experimental observations reported earlier and simulations of mycelial growth, carried out using a probabilistic‐geometric growth model developed for the purpose, both validate the applicability of the fractal model. In experiments with three different species, the fractal dimensions of pelletous structures were found to be in the range 1.45–2.0 and those of filamentous structures were in the range 1.9–2.7, with values around 2.0 representing mixed morphologies. Fractal dimensions calculated from simulated mycelia are in rough agreement with these ranges. The fractal dimension is also found to be relatively insensitive to the biomass concentration, as seen by dilution of the original broths. The relation between morphology and filtration properties of the broths has also been studied. The fractal dimension shows a strong correlation with the index of cake compressibility and with the Kozeny constant, two filtration parameters that are known to be morphology dependent. This technique could thus be used to develop correlations between the morphology, represented by the fractal dimension, and important morphology‐dependent process variables. © 1993 John Wiley&S

ISSN:0006-3592    

DOI:10.1002/bit.260420504

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractMany potential applications of primary hepatocytes cultured on microcarriers, such as an artificial liver or hepatocyte transplantation, would benefit from having a large number of hepatocytes attached to each microcarrier. In addition, the supply of primary hepatocytes is usually limited, so the efficient utilization of hepatocytes during attachment to microcarriers is necessary. Several physical parameters involved in the attachment process have been investigated, and the number of cells attached per microcarrier and the fraction of hepatocytes which attach have been quantitatively monitored. Variation of the partial pressure of gas phase oxygen in the incubation flask produced significant effects on the attachment of hepatocytes to microcarriers, with higher partial pressures of oxygen found to be necessary for attachment. In addition, variation of fluid depth and cell number, both of which influence the partial pressure of oxygen at the cell surface, affected hepatocyte attachment. The partial pressure of oxygen at the cell surface as a function of the physical parameters was analyzed using a simple one‐dimensional theoretical model. Variations in the cell‐to‐microcarrier ratio used for incubation indicate that a compromise must be made in terms of maximizing the number of cells per microcarrier and the fraction of total hepatocytes which attach. The maximum number of hepatocytes per microcarrier obtained in this work was approximately 100. The best attachment fraction, defined as the ratio of the number of hepatocytes attached to the total number added to the incubation, was approximately 90%. © 1993 John Wiley&Son

ISSN:0006-3592    

DOI:10.1002/bit.260420505

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe microbial degradation of quinoline byComamonas acidovoranswas studied in a laboratory scale stirred tank reactor. In continuous culture experiments using quinoline as a sole source of carbon and nitrogen, it was shown by means of mass balances that quinoline was converted completely to biomass, carbon dioxide, and ammonia. Degradation rates up to 0.7 g/L h were obtained. Measured yield coefficientsYx/sfor quinoline were about 0.7 g/g, which is in agreement with the theoretical value for complete mineralization. Kinetic constants based on Haldane substrate inhibition were evaluated. The values were μmax= 0.48 h−1,Ki= 69 mg/L, andKs<1.45 mg/L. © 1993 John Wiley&Sons,

ISSN:0006-3592    

DOI:10.1002/bit.260420506

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractProtein extractions using aerosol OT (AOT)–isooctane reverse micelle solutions have been studied to explore the potential for separating and enriching proteins with the reversed micellar extraction. The effects of pH, ionic strength, and different cations of chlorides in a bulk aqueous phase and of AOT concentration in an organic phase on the partitioning of lysozyme and myoglobin and the solubilization of water are presented in detail. The extraction of lysozyme was affected by the concentration of potassium or barium but was almost independent of that of sodium or calcium, whose ionic diameter is smaller than that of potassium and barium. For the extraction of myoglobin, however, the effect of barium concentration was not appreciable. Lysozyme could be enriched into the reversed micellar phase up to 30 times the aqueous feed concentration. © 1993 John Wiley&Sons, I

ISSN:0006-3592    

DOI:10.1002/bit.260420507

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractMuch of the current cell technology has enabled increased antibody production levels due to judicious nutrient feeding to raise cell densities and design better bioreactors. This study demonstrates that hybridomas can be hyperstimulated to produce higher immunoglobulin (lg) levels by suppressing cell growth and increasing culture longevity through adaptation to higher osmolarity media and addition of sodium butyrate. Prior to adaptation, cells placed in higher osmotic pressures (350 and 400 mOsm) were severely suppressed in growth down to 25% of the control (300 mOsm), although total lg titers achieved were similar to the control, approximately 140 mg/L. After a week of adaptation to 350 and 400 mOsm media, cell growth was not as dramatically suppressed, but considerably higher lg levels were attained at these elevated osmolarities. The highest yield of 265 mg/L was obtained at 350 mOsm compared to 140 mg/L at 300 mOsm, while maximum viable cell numbers dropped from 35 × 105cells/mL to 31 × 105cells/mL and culture longevity was extended by 20 h more than the control. Sodium butyrate, known to enhance protein production in other cell types, was then supplemented at a range of concentrations between 0.01 and 0.4 mM to the 350 mOsm culture to further enhance the lg levels. Butyrate at a concentration of 0.1 mM, in combination with osmotic pressure at 350 mOsm, further elevated the lg levels to 350 mg/L. Concomitantly, maximum viable cell numbers were reduced to 22 × 105cells/mL, but culture longevity was extended by 40 h in the 0.1 mM butyrate supplemented culture compared to the control condition. Specific antibody productivity, qMab, continued to stay high during the stationary phase and was further elevated during the decline phase: thus, overall lg levels can be increased by 2.3 times by combining osmotic pressure and butyrate treatment. © 1993 John Wiley&Sons,

ISSN:0006-3592    

DOI:10.1002/bit.260420508

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe effect of surfactants on the heterogeneous enzymatic hydrolysis of Sigmacell 100 cellulose and of steam‐exploded wood was studied. Certain biosurfactants (sophorolipid, rhamnolipid, bacitracin) and Tween 80 increased the rate of hydrolysis of Sigmacell 100, as measured by the amount of reducing sugar produced, by as much as seven times. The hydrolysis of steam‐exploded wood was increased by 67% in the presence of sophorolipid. At the same time, sophorolipid was found to decrease the amount of enzyme adsorbed onto the cellulose at equilibrium. Sophorolipid had the greatest effect on cellulose hydrolysis when it was present from the beginning of the experiment and when the enzyme/cellulose ratio was low. © 1993 John Wiley&Sons,

ISSN:0006-3592    

DOI:10.1002/bit.260420509

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe enantioselective esterification of racemic ibuprofen, catalyzed by aCandida cylindracealipase, was studied in a water‐in‐oil microemulsion (AOT/isooctane). By usingn‐propanol as the alcohol, an optimalW0([H2O]/[AOT]ratio) of 12 was found for the synthesis ofn‐propyl‐ibuprofenate at room temperature. The lipase showed high preference for theS(+)‐enantiomer of ibuprofen, which was esterified to the correspondingS(+)‐ibuprofen ester. TheR(−)‐ibuprofen remained unesterified in the microemulsion. The calculated enantioselectivity value (E) forS‐ibuprofen ester was greater than 150 (conversion 0.32). The enzyme activities ofn‐alcohols with different chain lengths (3–12) were compared, and it appeared that short‐ (propanol and butanol) and long‐chained (decanol and dodecanol) alcohols were better substrates than the intermediate ones (pentanol, hexanol, and octanol). However, unlike secondary and tertiary alcohols, all of the tested primary alcohols were substrates for the lipase. The reversible reaction (i.e., the hydrolysis of racemic ibuprofen ester in the microemulsion) was also carried out enantioselectively by the enzyme. Only theSform of the ester was hydrolyzed to the correspondingS‐ibuprofen. The reaction yield was, however, only about 4% after 10 days of reaction. The corresponding yield for the esterification of ibuprofen was about 35% (10 days). The high enantioselectivity displayed by the lipase in the microemulsion system was seen neither in a similar esterification reaction in a pure organic solvent system (isooctane) nor in the hydrolysis reaction in an aqueous system (buffer). TheEvalue forS‐ibuprofen ester in the isooctane system was 3.0 (conversion 0.41), and only 1.3 forS‐ibuprofen in the hydrolysis reaction (conversion 0.32). The differences in enantioselectivity for the lipase in various systems are likely due to interfacial phenomena. In the microemulsion system, the water in which the enzyme is dissolved is separated from the solvent by a layer of surfactant molecules, thus creating an interface with a relatively large area. Such interfaces are not present in the pure organic solvent systems (no surfactant) nor in aqueous sys

ISSN:0006-3592    

DOI:10.1002/bit.260420510

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY

摘要:

AbstractThe fatty acid production characteristics of fungi are described. These characteristics are the relationship between the oil content of the cell and the fatty acid content of the oil. For example, for polyunsaturated fatty acid (PUFA) production byMucor hiemalisIPD 51, the oil content of the cell and the GLA content of the oil are coupled. For fungal production of some PUFA, synthesized after the rate‐limiting step in the fatty acid anabolic chain, a maximum fatty acid production model was developed to link the fatty acid content of the oil and the oil content of the cell. Maximum volumetric productivity of gamma linolenic acid (GLA) by molds was found to occur at a specific GLA content of the oil. For example, forM. hiemalisIPD 51, a maximum volumetric of 4.7 mg GLA/L · h was produced at a GLA content of the oil of 8% to 10%. Similarly forMucor circinelloides v. TieghemIPD 155 a maximum volumetric productivity of 4.8 mg GLA/L · h was produced at a GLA content of the oil of 14% to 16%. These results imply that, when screening microorganisms for GLA or other fatty acid production, a number of medium compositions need to be evaluated to determine the tradeoff between oil content of the cell and fatty acid content of the oil. © 1993 John Wiley&Sons,

ISSN:0006-3592    

DOI:10.1002/bit.260420511

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1993

数据来源: WILEY