Use of biocatalysts

The use of biocatalysts for the selective introduction and cleavage of esters is vast and has been extensively reviewed." Therefore only a few examples of the types of transformations that are encountered in this area of protective group chemistry will be illustrated to show some of the basic transformations that have appeared in the literature. The selective... 

After discussing the biological capability to transform steroids, we briefly examine foe biotransformation of other terpenoids to ensure that the reader develops an awareness of the potential of biotechnology to modify or produce derivatives of a wide range of natural materials that are of tremendous potential, commercial value in the food and health care sectors. We also include a brief consideration of the use of biocatalysts to transform a range of other hydrocarbon compounds. 

Special reactors are required to conduct biochemical reactions for the transformation and production of chemical and biological substances involving the use of biocatalysts (enzymes, immobilised enzymes, microorganisms, plant and animal cells). These bioreactors have to be designed so that the enzymes or living organisms can be used under defined, optimal conditions. The bioreactors which are mainly used on laboratory scale and industrially are roller bottles, shake flasks, stirred tanks and bubble columns (see Table 1). 

The biotransformation process has been improved by significant advances in biochemical engineering advances in genetic and protein engineering, microbiological manipulations for the production of enzymes, and the use of biocatalysts in immobilized form and large-scale purification methods. 

A BDS patent [106] was awarded for the use of biocatalysts belonging to the group of Pseudomonas, Flavobacterium, Enterobacter, Aeromonas, Bacillus, or Corynebac-terium. One of the strains P. putida was further developed by mutation of the parent strain to obtain organic solvent-resistant mutants [107], The mutated strains were screened by selective cultivation in the presence of 0.1% to 10% by volume (v/v) of concentrations of a toxic organic solvent. The specific mutated strains obtained were P. putida No. 69-1 (PERM BP-4519), P. putida No. 69-2 (PERM BP-4520), and P. putida No. 69-3 (PERM BP-4521). 

The use of additional membranes, which selectively convert nonionic analytes into ionic species that can be determined via ISEs is another common approach. An abundance of ingenious designs make use of biocatalysts for the development of potentiometric biosensors. Much of the earlier designs have made use of enzymes as the molecular recognition element. The products that are associated with such enzyme-catalyzed reactions can be readily monitored with the potentiometric transducer by coating the traditional electrodes with the enzyme. 

Biocatalysis is still an emerging field hence, some transformations are more established than others.Panke et alP have performed a survey of patent applications in the area of biocatalysis granted between the years 2000 and 2004. They found that although hydrolases, which perform hydrolyses and esterifications, still command widespread attention and remain the most utilized class of enzyme (Figure 1.5), significant focus has turned towards the use of biocatalysts with different activities and in particular alcohol dehydrogenases (ADHs) - also known as ketoreductases (KREDs) - used for asymmetric ketone reduction. 

DuPont and Shell have developed a new polyester, poly(trimethylene terephthalate) (PTT) (structure 19.38) that is structurally similar to PET, except that 1,3-propanediol (PDO) is used in place of ethylene glycol. The extra carbon in Sorona allows the fiber to be more easily colored giving a textile material that is softer with greater stretch. Further, it offers good wear and stain resistance for carpet use. The ready availability of the monomer PDO is a major consideration with efforts underway to create PDO from the fermentation of sugar through the use of biocatalysts for this conversion. Sorona and Lycra blends have already been successfully marketed. Sorona is also targeted for use as a resin and film. 

A new technology, such as the use of biocatalysts, provides new entry opportunities for companies wishing to move into new prodnct areas. 

Many applications of biocatalysts are now matnre and so growth of only a few percent per year can be expected. Snbstantial growth can still be expected in new areas snch as the use of biocatalysts in bioorganic syntheses or in paper and pulp treatment. 

Use of biocatalysts in combination with other separate chemical steps. aspartame, (S)-2-chloropropanoic acid, L-PAC... 

Table 13.1 Some commercial driving forces for the use of biocatalysts.

In the context of this chapter biocatalysis is the use of enzymes or enzymes still associated with their parent cells, to carry out defined chemical reactions under controlled conditions, so as to efficiently convert raw materials into commercially more valuable products. Some of the commercial driving forces for the use of biocatalysts are listed in Table 13.1. 

Biocatalytic asymmetric oxidations were developed very early for key steps in the production of vitamin C [9] and steroid hormones [10] and for a series of applications in organic synthesis [8], as illustrated in Figure 20.2. The use of biocatalysts in oxidation reactions is growing [11-15] and the inherent chirality of the enzymes enables a wide variety of biocatalytic asymmetric oxidations, an overview of which is given in the next six sections. 

Although prochiral or chiral alcohols and carboxylic acid esters initially served as the primary classes of substrates, compounds susceptible to processing via these two routes now encompass diols, a- and 3-hydroxy acids, cyanohydrins, chlorohydrins, diesters, lactones, amines, diamines, amino alcohols, and a-and 3-amino acid derivatives. Gotor and Arroyo have reviewed the use of biocatalysts for the preparation of pharma-eeutical intermediates and fine ehemieals. Some specific examples are indieated below. 

Table 2.14 gives an overview of industrial processes using asymmetric catalysis, including examples both of asymmetric hydrogenation and other types of reactions, as well as of the use of biocatalysts for the reaction. Selected chiral ligands used in asymmetric catalytic reactions are also shown in the table. 

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