Biotransformations systems

Several experiments using different organic solvents in different biphasic media are necessary to find the adequate distribution of the reaction components. A series of experiments are essential for the choice of a process and for scaling-up. Experiments using Lewis cells [44] may yield useful results for understanding equilibrium, kinetics, and interactions between organic solvent-substrate and/or organic solvent-biocatalyst. A study of two-liquid phase biotransformation systems is detailed below in Sections II-IX. 

One of the main obstacles for whole-cell microbial transformation in an organic solvent is its biocompatibility, which has led to screening for organic-solvent-tolerant microorganisms. Numerous organic-solvent-tolerant microorganisms have been found and their tolerance mechanisms have been reviewed [14,33,34]. Two-phase biotransformation systems have been successfully implemented for the production of pharmaceutically relevant metabolites. 

Chambers, J. E., Yarbrough, J. D. Xenobiotic biotransformation systems in fishes. Comp. Bioahem. Physiol. (1976)... 

The biotransformation systems involved in insecticide metabolism have been studied in the R and S populations to determine any differences which might be potential contributory factors to or results of insecticide resistance. In addition, the possibility of mixed-function oxidase induction has been investigated. Specifically, the studies have encompassed a seasonal study of microsomal mixed-function oxidase (mfo) components, and studies of aldrin, dieldrin and DDT metabolism. 

The notion that enzymes might well function in apolar solvents has been explored in detail and confirmed by Klibanov and his followers during the past two decades.Similarly, many microorganisms have been found to grow well in the presence of bulk solvents. " This has permitted the development of biotransformation systems in which water-insoluble compounds are dissolved in apolar phases, to be converted to products by whole cells present in an aqueous phase, the products generally then dissolving again in the apolar phase. 

New supramolecular compounds mimicking biological cofactors have been proposed which have high redox potentials and, further, can be Hnked covalently onto supports in biotransformation systems [52]. Bioelectrochemical methods available for regeneration of nicotinamide- and flavin-dependent systems are comprehensively reviewed by Kohhnan et al. [53]. 

In a biotransformation system designed to mediate the o-dealkylation of 7-ethoxycumarin to 7-hydroxycoumarin, the genes for the P450 from Streptomyces peucelius and putidaredoxin reductase (CamA) and putidaredoxin (CamB) from... 

The model provides a good approach for the biotransformation system and highlights the main parameters involved. However, prediction of mass transfer effects on the outcome of the process, through evaluation of changes in the mass transfer coefficients, is rather difficult. A similar mass transfer reaction model, but based on the two-film model for mass transfer for a transformation occurring in the bulk aqueous phase as shown in Figure 8.3, could prove quite useful. Each of the films presents a resistance to mass transfer, but concentrations in the two fluids are in equilibrium at the interface, an assumption that holds provided surfactants do not accumulate at the interface and mass transfer rates are extremely high [36]. 

Figure 8.3 Two-liquid film model adapted to a biotransformation system where substrate and product are hydrophobic and reaction occurs in the bulk aqueous phase.

Singh A, Singh SP, Bamezai R. 1995. Postnatal modulation of hepatic biotransformation system enzymes via translactational exposure of FI mouse pups to turmeric and curcumin. Cancer Lett 96 87-93. 

The initial activation of compounds is catalysed by various enzymes, depending on the chemical structure of the compound in question. The cytochrome P450 monooxygenase complex (CYP) is the major biotransforming system. In vertebrates it is present in all the organs of the body and particularly abundant in the liver. 

This monophasic biotransformation system was used for the hydroxylation of 2,2 -dihydroxybiphenyl to 2,2, 3-trihydroxybiphenyI within a reaction time of 2.5 h and 2.2. 3,3 -tetrahydroxybiphenyl after 23 h. A mean volume productivity of 0.43 and 0.05 g l-1 h 1, respectively, was achieved for these biotransformations. Furthermore, HbpA and FDH were applied in 80 vol.% decanol to hydroxylate 2-hydroxybiphenyl to 2,3-dihydroxybiphenyl with a productivity of 0.46 g 1 1 h 1 and a total turnover number of 503. In 10 vol.% aqueous methanol the total turnover number of 30 and enzyme stability for at least 60 h were observed. Because of the... 

The availability of ready for use nitrilase preparations [41] with the advantage of avoiding the laborious handling of whole cell biotransformation systems has simplified the reaction protocol substantially and prompted the screening of nitrilases... 

The xenobiotic-related induction of the biotransformation system usually leads to an initial adaptive response hyperplasia of the SER (= smooth endoplasmic reticulum) occurs, (s. pp 55, 394, 524) (s. fig. 21.2) The cytoplasm takes on the turbid appearance of opalescent glass. These ground glass hepatocytes (s. pp 114, 396, 424) (s. figs. 5.7 22.8) are not produced by all foreign substances,... 

The appropriateness of the in vitro system depends on the relevance of the system for the exposure in the intact organism that needs to be predicted, the stability of the system over time, and the physiologically correct balance between the formation and further metabolism of reactive intermediates. Thus, if a repeated-dose exposure for humans is to be predicted, the appropriate system would be a system that is relevant for the human biotransformation system, and take into account the time of exposure as well as the fluctuations in blood concentrations, e.g., resulting from a daily single dose [41], Examples of such studies taking this into account were carried out in the EU program Predict-IV [42, 43],... 

Saving a biotransformation in the system stores all relevant data in the main database (administrative data, connectivity information) and in the chemistry databases (strnctnre, spectra, other instrnmental data and metadata). Optionally, the biotransformation system may be integrated with an electronic notebook solntion. When started from the notebook, the biotransformation system creates a graphical representation of the metabolic pathway and sends it together with administrative data and metadata to an electronic scientific docnment. 

Metadata are an important concept of the biotransformation system. They provide additional information abont data objects and can be customized. Metadata consist at least of a name and a value. They may additionally contain flags, which describe special conventions for processing of metadata with the software. Administrators of the biotransformation system may define a set of metadata for a series of data types by name and default value. In addition, the user is able to define lists of metadata that can be used in certain visible list fields, like dropdown lists. 

A fish swimming in a lake with uptake through the gills and elimination through just one biotransformation system, for instance, by an enzyme in the liver, may be regarded as a one-compartment system ... 

Hyotylainen T, Oikari A. 1999a. Assessment of the bioactivity of creosote-contaminated sediment by liver biotransformation system of rainbow trout. Ecotoxicol Environ Saf 44 253-258. 

Spore suspension— Because spores contain many unique enzymes not expressed in other forms of the organism and because they are relatively stable and active in buffer over a long period of time, spore suspensions are often useful biotransformation systems (see Note 8). 

Fixation of plant cells in a matrix of, for example, polyurethane foam or entrapment of the cells in calcium alginate beads provides an artificial surrounding for the cells, which protects them from hydrodynamic stress, high cell densities inside the matrix also allow cell to cell contact and communication. Inside the immobilized matrix nutrient and product gradients may occur. Furthermore, immobilized biomass is easily separated from the medium, which is useful in production and biotransformation systems. Immobilization of plant cells has been reviewed 103,104). 

Singh, A., S.P. Singh, and R. Bamezai. 1996. Effect of arecoline on the curcumin-modulated hepatic biotransformation system enzymes in lactating mice and translactationally exposed Fj pups. Nutr. CflHcer 25(1) 101-110. 

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