Enzyme membrane reactors discussion

The enzyme membrane reactor (EMR) is an established mode for running continuous biocatalytic processes, ranging from laboratory units of 3 mL volume via pilot-scale units (0.5-500 L) to full-scale industrial units of several cubic meters volume and production capacities of hundreds of tons per year (Woltinger, 2001 Bommarius, 1996). The analogous chemzyme membrane reactor (CMR) concept, discussed in Chapter 18, Section 18.4.5, is based on the same principles as the EMR but is far less developed yet. 

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 overall mass-transfer rates on both sides of the membrane can only be calculated when we know the convective velocity through the membrane layer. For this, Equation 14.2 should be solved. Its solution for constant parameters and for first-order and zero-order reaction have been given by Nagy [68]. The differential equation 14.26 with the boundary conditions (14.28a) to (14.28c) can only be solved numerically. The boundary condition (14.28c) can cause strong nonlinearity because of the space coordinate and/or concentration-dependent diffusion coefficient [40, 57, 58] and transverse convective velocity [11]. In the case of an enzyme membrane reactor, the radial convective velocity can often be neglected. Qin and Cabral [58] and Nagy and Hadik [57] discussed the concentration distribution in the lumen at different mass-transport parameters and at different Dm(c) functions in the case of nL = 0, that is, without transverse convective velocity (not discussed here in detail). 

The discussion about the choice of an appropriate reactor and optimized operation conditions will be continued in Sect. 7.5.2.1. Anticipating the results, the reaction can be performed effectively under the above reaction conditions in an enzyme membrane reactor yielding a product with an enantiomeric purity of higher than 99%. 

In the preceding section, we analyzed an immobilized enzyme process and calculated some important parameters such as productivity. In this section, we investigate another process configuration for retaining biocatalysts, the membrane reactor. The advantages and disadvantages of immobilization and membrane retention have already been discussed in Chapter 5. As in the case of immobilization, retention of catalyst by a membrane vastly improves biocatalyst productivity, a feature important on a processing scale but usually not on a laboratory scale. 

Speaking about biotechnology the topics of the use of membrane reactors and the filtration of yeast, enzymes and proteins are discussed most often. Sometimes it is difficult to discern biotechnology from applications in more established industries like dairy, etc. Besides that, in many papers biotechnology is mentioned in a rather general sense [6,11,85-87], perhaps indicating the freshness of these processes and/or some reluctance in communicating details about the application. 

There is no commonly accepted definition of a membrane reactor but the term is applied to membrane (including liquid membrane) processes and devices whose function is to perform chemical conversion, coupling and combining chemical and transport processes, using the unique contacting features of membranes. As a rule, functional definition of this term includes fermentation, catalysis, separation of the products and their enrichment. A few published reviews at this time are available [98-104]. In most of pubhcations the bioreactors, based on enzymes or whole cells, impregnated into the membrane pores (immobihzed or supported hquid membranes) or deposited on the membrane surfaces are discussed. 

Discussion of methods, substrate synthesis, continuous process, membrane reactor, enzyme deactivation Development phases, route comparison, test of many alternative methods, technical catalyst preparation, process optimization, ee enrichment via crystallization, industrial assessment... 

The modelling of enzymatic membrane reactors follows, in general, the same approach as described previously. In enzymatic membrane reactors the catalyst is a macromolecule (enzyme). It can be found either in a free form in the reactor or supported on the membrane surface, or inside the membrane porous structure by grafting it or in the form of a gel obtained by ultrafiltration. As in the case of the whole-cell membrane bioreactors discussed above, the proper calculation of the mass transfer characteristics is of great importance for the modelling of this type of reactor. One of the earliest models of enzymatic membrane bioreactors is by Salmon and Robertson [5.108]. These authors modelled an enzymatic membrane bioreactor, which was made of four coaxial compartments the enzyme is confined within one of the compartments, and one of the substrates is fed in a gaseous form. 

Molecular separation along with simultaneous chemical transformation has been made possible with membrane reactors [17]. The selective removal of reaction products increases conversion of product-inhibited or thermodynamically unfavourable reactions for example, in the production of ethanol from com [31]. Enzyme-based membrane reactors were first conceived 25 years ago by UF pioneer Alan Michaels [49]. Membrane biocatalytic reactors are used for hydrolytic conversion of natural polymeric materials such as starch, cellulose, proteins and for the resolution of optically active components in the pharmaceutical, agrochemical, food and chemical industries. Membrane bioreactors for water treatment were introduced earher in this chapter and are discussed in detail in Chapters 2 and 3. 

The principle of both membrane reactors and membrane bioreactors are the same but the origin is completely different. In the case of a bioreaction enzymes or microorganisms (bacteria, fungi, mammalian ceils, yeasts) are applied under very specific reaction conditions. Both concepts wil be discussed briefiy. 

The rising need for new separation processes for the biotechnology industry and the increasing attention towards development of new industrial eruyme processes demonstrate a potential for the use of liquid membranes (LMs). This technique is particularly appropriate for multiple enzyme / cofactor systems since any number of enzymes as well as other molecules can be coencapsulated. This paper focuses on the application of LMs for enzyme encapsulation. The formulation and properties of LMs are first introduced for those unfamiliar with the technique. Special attention is paid to carrier-facilitated transport of amino acids in LMs, since this is a central feature involved in the operation of many LM encapsulated enzyme bioreactor systems. Current work in this laboratory with a tyrosinase/ ascorbate system for isolation of reactive intermediate oxidation products related to L-DOPA is discussed. A brief review of previous LM enzyme systems and reactor configurations is included for reference. 

As was described above in a number of MBR processes the membrane, in addition to performing the separation functions previously discussed, also acts as a host for the biocatalysts (whole cells or enzymes) which are immobilized in the membrane s pore structure. Concerns with such MBR configurations include membrane biofouling, mass transport limitations and biocatalyst activity loss and denaturation. In the two sections that follow we discuss further some of the key aspects of MBR for biochemical synthesis. We classify these reactors into two types, namely whole-cell and enzymatic MBR. 

Changes in membrane resistance and electro-osmotic properties as salt redistributes play a critical role in the Teorell oscillator, so the membrane is an active player in the oscillation mechanism. Changes in membrane permeabihties to various species (including solvent and current carriers) also play a role in most of the nonen2ymatic oscillators discussed. We also showed that the membrane can act simply to limit transport into and out of a reactor, with the membrane s own properties remaining constant - the PFK system is exemplary of this limit Here, the membrane s selectivity to different reactants contributes to oscillatory behavior. In the discussion of the hydrogel-enzyme system in the next section, the membrane and enzyme behaviors are seen to be mutually coupled, and the most significant transitions occur inside the membrane. 

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