Membrane Extraction Integrated Systems

An example of an industrial membrane bioreactor is the hollow-fiber membrane system for the production of (-)-MPGM (1), which is an important intermediate for the production of diltiazem hydrochloride [130, 131]. For the enantiospecific hydrolysis of MPGM a hoUow-fiber ultrafiltration membrane with immobilized lipase from Serratia marcescens is used. (-i-)-MPGM is selectively converted into (2S,3R)-(-i-)-3-(4-methoxy-phenyl)glycidic acid and methanol. The reactant is dissolved in toluene, whereas the hydrophilic product is removed via the aqueous phase at the permeate side of the membrane (see Fig. 5.17). Enantiomerically pure (-)-MPGM is obtained from the toluene phase by a crystallization step. In cooperation with Sepracor Inc., a pilot-plant membrane reactor has been developed, which produces annually about 40 kg (-)-MPGM per m of membrane surface. 

In a comparable system, (R,S)-ibuprofen can be separated by a membrane reactor [132] (see Fig. 5.18). The technique comprises a stereospecific hydrolysis by an enzyme. Subsequently, the enantiomeric ester is extracted into the organic phase on the other side of the membrane. In the system developed by Sepracor Inc., (R)-ibuprofen is selectively hydrolyzed by proteases in a hollow-fibre unit and the (S)-ibuprofen ester can be isolated at 100% yield. This configuration also applies for enantioseparation of other acids such as naproxen and 2-chloro-propionic acid. 

Although at the moment no large-scale method exists for the production of enantiomerically pure components, it can be foreseen that both the MPGM and Sepracor reactor system have potential for application on a larger scale due to their ease of scale-up. 

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Wodski R and Szczepaiiski P. Integrated hybrid membrane systems—membrane extraction and pertraction coupled to a pervaporation process. J. Membr. Sci. 2002 197 297-308. 

After extraction, the solute-laden CLAs need to be separated from the mother liquor so that they can be back stripped. Hence attempts were made to filter the solute-rich CLAs from the aqueous phase using cross-flow microfiltration [70]. The filtration characteristics of the CLAs as indicated by the flux, CLA size, and concentration showed that they are completely retained by the membrane and do not foul the membrane surface. Using this system, the CLAs could easily be concentrated up to 30% w/v at low pressures, and the permeate stream remained totally clear. The CLAs appear to maintain their structural integrity because only 3 mg dm of SDS was... 

Thus, the fat globules are surrounded, at least initially, by a membrane typical of eukaryotic cells. Membranes are a conspicuous feature of all cells and may represent 80% of the dry weight of some cells. They serve as barriers separating aqueous compartments with different solute composition and as the structural base on which many enzymes and transport systems are located. Although there is considerable variation, the typical composition of membranes is about 40% lipid and 60% protein. The lipids are mostly polar (nearly all the polar lipids in cells are located in the membranes), principally phospholipids and cholesterol in varying proportions. Membranes contain several proteins, perhaps up to 100 in complex membranes. Some of the proteins, referred to as extrinsic or peripheral, are loosely attached to the membrane surface and are easily removed by mild extraction procedures. The intrinsic or integral proteins, about 70% of the total protein, are tightly bound to the lipid portion and are removed only by severe treatment, e.g. by SDS or urea. 

Many of the metabolite uptake studies cited above rely on combined uptake and incorporation into starch. In order to separate uptake from incorporation, Schott et al.226 extracted amyloplast membrane proteins from potato tubers and reconstituted them into liposomes. These reconstituted liposomes transported Pi, triose phosphates and G6P in a counter-exchange mode. The liposomes were ineffective in the transfer of G1P uptake of ADP-Glc was not tested. Mohlmann et al.236 have used a proteoliposomic system to reconstitute plastid envelope proteins. In this system, ADP-Glc is transported in exchange for AMP. Thus the more widely studied plastid ATP/ADP transporter was not responsible for ADP-Glc uptake. More recently, Bowsher et al.237 reported that wheat endosperm amyloplasts membrane proteins reconstituted into proteoliposomes took up ADP-Glc in exchange for AMP and ADP. In addition, they showed that under conditions of ADP-Glc dependent starch biosynthesis, the efflux of ADP from intact amyloplasts was equal to that of ADP-Glc utilization by starch synthesis. The amyloplast membrane ADP-Glc/ADP transporter was a 38 000 molecular weight integral membrane protein.237... 

Two main criteria for the membrane selection are pore size and material. As peroxidases usually have sizes in the range of 10-80 kDa, ultrafiltration membranes with a molecular cutoff between 1 and 50 kDa are the most adequate to prevent enzyme leakage [99]. The materials commonly applied to ultrafiltration membranes are synthetic polymers (nylon, polypropylene, polyamide, polysulfone, cellulose and ceramic materials [101]. The adequate material depends on a great number of variables. When enzyme is immobilized into the matrix, this must be prepared at mild conditions to preserve the enzymatic activity. In the case of enzyme immobilization onto the membrane, this should be activated with the reactive groups necessary to interact with the functional groups of the enzyme. If an extractive system is considered, the selection of the hydrophilicity or hydro-phobicity of the membrane should be performed according to the features of reactants, products, and solvents. In any case, the membrane should not interfere with the catalytic integrity of the enzyme. 

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