Membrane bioreactors enzyme

As an immobilization method, both for whole cells or enzymes, membrane bioreactors provide the advantages and drawbacks common to entrapment or adsorption methods. They nevertheless present particular assets. Mass transfer in the porous supports generally used (alginate, k-carrageenan, zeolites, silica) is a diffusion-controlled process, often becoming the overall rate-limiting step. This maybe overcome by the use of membrane modules. This equipment also avoids... 

An enzyme membrane bioreactor can be created in different configurations the membrane can be used in order to confine or separate the biocatalyst from the reaction mixture furthermore, membranes can be used as a support for biocatalysts (enzymes or whole cells) immobilization. 

Membrane-based separation, lactic acid production and, 14 120 Membrane biocompatibility, in hemodialysis, 26 823—824 Membrane bioreactors, 16 26 Membrane-bound enzymes, 10 338 Membrane cell process, 9 620 Membrane cells... 

In the development of cell or enzyme-based processes, many process configurations exist, including batch, fed batch and continuous operation. In general, the conversion and the separation processes (downstream processing) are regarded as separate units, and most industrial processes are based on this approach. In the last decades, however, more attention is paid to the integration of conversion and separation, leading to the development of membrane bioreactors [49, 50], and some of these concepts have reached an industrial scale. The membranes used for this type of reactors are almost exclusively polymeric, as temperatures seldomly exceed 100 °C for obvious reasons. 

Generally, a distinction can be made between membrane bioreactors based on cells performing a desired conversion and processes based on enzymes. In ceU-based processes, bacteria, plant and mammalian cells are used for the production of (fine) chemicals, pharmaceuticals and food additives or for the treatment of waste streams. Enzyme-based membrane bioreactors are typically used for the degradation of natural polymeric materials Hke starch, cellulose or proteins or for the resolution of optically active components in the pharmaceutical, agrochemical, food and chemical industry [50, 51]. In general, only ultrafiltration (UF) or microfiltration (MF)-based processes have been reported and little is known on the application of reverse osmosis (RO) or nanofiltration (NF) in membrane bioreactors. Additionally, membrane contactor systems have been developed, based on micro-porous polyolefin or teflon membranes [52-55]. 

A key consideration in development of all multi-step bioprocesses is the type of bioreactor it may be necessary to accommodate a range of conditions including compartmentalization of the enzymes, cofactor recycle, adequate oxygen supply, variable temperature and pH requirements, and differential substrate feed rates. Examples described below include a range of different reactors, of which membrane bioreactors are clearly often particularly useful. 

A liquid membrane bioreactor was developed as a means of encapsulation for a multi-enzyme system incorporating an oxidation and carbohydrate cleavage, demonstrated using a-glucosidase and glucose oxidase in the conversion of maltose to gluconic acid ... 

Figure 11.9 Different arrangements and modes of operation for membrane bioreactors Continuous Stirred Tank Reactor (CSTR) with recirculation arrangement (a), dead-end cell (b), tubular with entrapped enzyme (c).

The possibility of having membrane systems also as tools for a better design of chemical transformation is today becoming attractive and realistic. Catalytic membranes and membrane reactors are the subject of significant research efforts at both academic and industrial levels. For biological applications, synthetic membranes provide an ideal support to catalyst immobilization due to their biomimic capacity enzymes are retained in the reaction side, do not pollute the products and can be continuously reused. The catalytic action of enzymes is extremely efficient, selective and highly stereospecific if compared with chemical catalysts moreover, immobilization procedures have been proven to enhance the enzyme stability. In addition, membrane bioreactors are particularly attractive in terms of eco-compatibility, because they do not require additives, are able to operate at moderate temperature and pressure, and reduce the formation of by-products. 

Membrane bioreactors have been reviewed previously in every detail [3,4,7,8,18], There are two main types of membrane bioreactors (i) the system consists of a traditional stirred-tank reactor combined with a membrane separation unit (Figure 14.1) (ii) the membrane contains the immobilized biocatalysts such as enzymes, micro-organisms and antibodies and thus, acts as a support and a separation unit (Figure 14.2). The biocatalyst can be immobilized in or on the membrane by entrapment, gelification, physical adsorption, ionic binding, covalent binding or crosslinking [3, 7, 18]. Our attention will be primarily focused on the second case where the membrane acts as a support for biocatalyst and as a separation unit, in this study. The momentum and mass-transport process, in principle, are the same in both cases, namely when there is... 

Figure 14.2 Membrane bioreactor with immobilized biocatalysts (enzyme or micro-organism).

Applications of whole-cell biocatalytic membrane reactors, in the agro-food industry and in pharmaceutical and biomedical treatments are listed by Giorno and Drioli [3], Frazeres and Cabral [9] have reviewed the most important applications of enzyme membrane reactors such as hydrolysis of macromolecules, biotransformation of lipids, reactions with cofactors, synthesis of peptides, optical resolution of amino acids. Another widespread application of the membrane bioreactor is the wastewater treatment will be discussed in a separate section. 

The modeling of membrane bioreactors is in the initial stage. There are not available more or less sophisticated mathematical tools to describe the complex biochemical processes. It is not known how the mass-transport parameters, diffusion coefficients, convective velocity, biological kinetic parameters might vary in function of the operating conditions, of the biolayer (enzyme/micro-organism membrane layer)... 

Membrane bioreactors have been reported for the production of diltiazem chiral intermediate with a multiphase/extractive enzyme membrane reactor [15, 16]. The reaction was carried out in a two-separate phase reactor. Here, the membrane had the double role of confining the enzyme and keeping the two phases in contact while maintaining them in two different compartments. This is the case of the multiphase/ extractive membrane reactor developed on a productive scale for the production of a chiral intermediate of diltiazem ((2R,3S)-methylmethoxyphenylglycidate), a drug used in the treatment of hypertension and angina [15]. The principle is illustrated in... 

One of the first cases of the application of membrane bioreactors in food processes was the production of milk with low lactose content. (3-galactosidase was entrapped into cellulose acetate fibers to carry out the hydrolysis of milk and whey lactose [2] recently the system was improved by the use of microfiltration and by UV irradiation of the enzyme solution to avoid growth of micro-organisms [45]. 

Membrane Bioreactors with Membrane as Bio reactor 310 Enzyme Membrane Reactor 311 Whole-Cell Membrane Bioreactor 312 Membrane Bioreactors with Membrane as Separation... 

Mathematical Modeling of Membrane Bioreactor 314 Modeling of Enzyme Membrane Layer/Biofilm Reactor 314... 

A more appropriate definition of membrane bioreactors confines them to devices in which biochemical conversion actually occurs. For example, an enzyme may be immobilized in the membrane by physical sorption or covalent... 

FIGURE 46 Membrane bioreactor in a multiphasic configuration with reversible enzyme containment. 

It is significant that the reaction mixture was worked up by removal of the unreacted ester by hexane extraction and concentration of the aqueous layer to obtain the desired (i )-amino acid. The process has a high throughput and was easy to handle on a large scale. However, because of the nature of a batch process, the enzyme catalyst could not be effectively recovered, adding significantly to the cost of the product. In the further scale up to 100-kg quantity productions, the resolution process was performed using Sepracor s membrane bioreactor module. The enzyme was immobilized by entrapment into the interlayer of the hollow-fiber membrane. Water and the substrate amino ester as a neat oil or hexane solution were circulated on each side of the membrane. The ester was hydrolyzed enantioselectively by the enzyme at the membrane interface, and the chiral acid product... 

FIGURE 6.5 Membrane bioreactor for enzyme catalyzed enantioselective hydrolysis of racemic ethyl 2-amino-2-ethylhexanoate. 

One of the major disadvantages of using these enzymes to reduce ketones is generally the very poor aqueous solubility of the substrates (usually <5-10 mM) and the fact that the co-factor regeneration system is sensitive to organic solvents. To address this limitation, biphasic and membrane bioreactors have been used that allow for moderate to high conversions with often >99% ee for selected products. This has been demonstrated with the (.S )-Adi I from Rhodococcus erythropolis,36-37... 

Prazeres DMF, Cabral JMS (1994) Enzymatic membrane bioreactors and their applications. Enzyme Microb Technol 16 738-750... 

There have been numerous studies exploring the concept of membrane reactors. Many of them, however, are related to biotechnological applications where enzymes are used as catalysts in such reactions as saccharification of celluloses and hydrolysis of proteins at relatively low temperatures. Some applications such as production of monoclonal antibodies in a hollow fiber membrane bioreactor have just begun to be commercialized. 

Figure 8.6 Schematic difference between an enzyme-immobilized column reactor and a forced-flow membrane bioreactor (Nakajima et al., 1988]...

Based on these observations, Wang and Caruso [237] have described an effective method for the fabrication of robust zeolitic membranes with three-dimensional interconnected macroporous (1.2 pm in diameter) stmctures from mesoporous silica spheres previously seeded with silicalite-1 nanoparticles subjected to a conventional hydrothermal treatment. Subsequently, the zeolite membrane modification via the layer-by-layer electrostatic assembly of polyelectrolytes and catalase on the 3D macroporous stmcture results in a biomacromolecule-functionalized macroporous zeolitic membrane bioreactor suitable for biocatalysts investigations. The enzyme-modified membranes exhibit enhanced reaction stability and also display enzyme activities (for H2O2 decomposition) three orders of magnitude higher than their nonporous planar film counterparts assembled on silica substrates. Therefore, the potential of such structures as bioreactors is enormous. 

Konovalova VV, Dmytrenko GM, Nigmatullin RR, Bryk MT, and Gvozdyak PL Chromium(Vl) reduction in a membrane bioreactor with immobilized Pseudomonas cells. Enzyme Microbial Technol, 2003 33(7) 899-907. 

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