Advantages and Disadvantages of Biocatalysts

What do yon consider to be the most important general advantages and disadvantages of enzyme and cell biocatalysts when used in large-scale processes, as compared with other production technologies snch as chemistry ... 

Conventional filters, such as a coffee filter, termed depth filters , consist of a network of fibers and retain solute molecules through a stochastic adsorption mechanism. In contrast, most membranes for the retention of biocatalysts feature holes or pores with a comparatively narrow pore size distribution and separate exclusively on the basis of size or shape of the solute such membranes are termed membrane filters . Only membrane filters are approved by the FDA for sterilization in connection with processes applied to pharmaceuticals. Table 5.3 lists advantages and disadvantages of depth and membrane filters. 

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. 

In general there are two principle possibilities using a biocatalyst in organic synthesis, namely as whole cells or as isolated enzymes - free or immobilized. The advantages and disadvantages of each can be intensively discussed, but the outcome of this consideration always depends on the whole system and the kind of application. There are numerous examples of both and thus there is no partitioning between whole cell biotransformation and isolated enzymes in this review. 

Describe in your own words the advantages and disadvantages of using whole cells compared to isolated enzymes as biocatalysts, with respect to catalyst immobilization, catalyst recovery, ease of use, and product selectivity and purification. 

Figure 15-21. Advantages and disadvantages of whole cell, isolated enzymes and recombinant cell as biocatalysts.

Cofactor recycling is no problem when whole microbial cells are used as biocatalysts for redox reactions. In this case, inexpensive sources of redox equivalents such as carbohydrates can be used since the microorganism possesses all the enzymes and cofactors which are required for metabolism. The advantages and disadvantages of using whole-cell systems are discussed in Sect. 2.2.3. 

The disadvantages of biocatalysts will now be considered, followed by their advantages. You should note that the pros and cons of biotechnology versus chemical synthesis are very general and that exceptions may exist. 

Enzymes show some advantages and disadvantages with other kinds of catalysts (Table 4-1). Whereas enzymes often exhibit great advantages in terms of selectivity, their stability is often insufficient. Furthermore, long development times of new biocatalysts remain a problem and a challenge. 

The transition between the soluble and insoluble state of stimuli-responsive polymers has been used to develop reversibly soluble biocatalysts. A reversibly soluble biocatalyst catalyzes an enzymatic reaction in a soluble state and hence could be used in reactions of insoluble or poorly soluble substrates/products. As soon as the reaction is completed and the products are separated, the conditions (pH, temperature) are changed to promote precipitation of the biocatalyst. The precipitated biocatalyst is separated and can be used in the next cycle after dissolution. The reversibly soluble biocatalyst acquires the advantages of immobilized enzymes (ease of separation from the reaction mixture after the reaction is completed and the possibility for biocatalyst recovery and repeated use in many reaction cycles) but at the same time overcomes the disadvantages of enzymes immobihzed onto solid matrices such as diflfusional limitations and the impossibility of using them in reactions of insoluble substrates or products. 

In summary, the synthesis and in situ regeneration of nucleotide sugars by combinatorial biocatalysis suffers from the main disadvantage that each enzyme has to be produced in sufficient amounts. This affords efficient recombinant protein produchon hosts being a bottleneck for some genes [25]. However, once a multi-enzyme system has been developed, the productivity can be improved by repetitive use of the biocatalysts as demonstrated for repetitive batch syntheses with soluble enzymes [25, 38] or with immobilized enzymes [48]. The advantage... 

In spite of the clear advantages, membrane-coupled processes often turn out to be still more expensive, because of the costs of membrane and all additional hardware associated with a membrane operation. Membrane separations tend to become more favorable for processes where the selectivity is more important than the conversion, because it replaces other purification steps that might lower such selectivities, like in the production of the chiral diltiazem intermediate. Membrane fouling, mass transfer limitations, biocatalyst activity loss, and biocatalyst denaturation are other potential disadvantages related to it. 

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