Biocatalysts, fine chemical reactions

The use of industrial enzymes for the synthesis of bulk and fine chemicals represents a somewhat specialized application for biocatalysts relative to their broader uses, as outlined above. Industrial biocatalysis is, however, becoming increasingly relevant within the chemical industry for the production of a wide range of materials (see Table 31.3).1,2,4-8 Broadly defined, a biocatalytic process involves the acceleration of a chemical reaction by a biologically derived catalyst. In practice, the biocatalysts concerned are invariably enzymes and are used in a variety of forms. These include whole cell preparations, crude protein extracts, enzyme mixtures, and highly purified enzymes, both soluble and immobilized. 

One of the areas to benefit from the speed and efficiency of reaction optimization afforded by continuous flow processes is that ofbiochemical transformations involving enzymes, whole cells, or lysates [78]. Biocatalysis is an important area of synthetic chemistry that has been extensively studied for application within industry for the synthesis of amino adds, lipids, sugars, pharmaceuticals, and fine chemicals however, the long-term instability of biocatalysts predudes application within industry. 

Since many enzymes have capacities to catalyze reactions with even unnatural substrates and to produce unnatural compounds, hybrid use of enzymes as biocatalysts with chemical synthesis can realize processes to produce useful substances with higher flexibility than processes with growing cells. Discovery of novel microbial enzymes with required specificity by screening is a key to the establishment of such a hybrid processes. Many successful achievements in Japan are observed in this unique field of biotechnology. Application of nitrile hydratase to production of acrylonitriles has proved that biocatalysts can be applied to production of commodity chemicals beyond the presumed limitation of fine chemicals. Discovery of the enzymatic reactions to produce trehalose from starch is an example that reveals the possibility of microbial screening or what remains undiscovered in the microbial world. The importance of developing new application is also crucial in this field as shown in the case of transglutaminase and alkaline cellulase. 

Lonza Fine Chemicals manufactures nicotinamide by a process in which 2-methyl-l,5-diaminopentane (a by-produa of nylon-6,6 manufacture) is first converted to 3-cyanopyridine 121 by a series of three chemically-catalyzed reactions, then the nitrile is hydrated to nicotinamide 122 (Figure 11.37) using Rhodococcus rhodochrous Jl cells immobilized in polyacrylamide particles [227-229]. A continuous feed of 3-cyanopyridine at concentrations of between 10-20 Avt /o is added in the direction of process flow, with a counter-current feed of biocatalyst in a series of stirred-tank batch bioreactors. The process generates... 

Transaminases are important enzymes in the synthesis of chiral amines, amino acids, and amino alcohols, hi this chapter the properties of transaminases, the reaction mechanisms, and their selectivity and substrate specificity are presented. The synthesis of chiral building blocks for pharmaceutically relevant substances and fine chemicals with transaminases as biocatalysts is discussed. Enzymatic asymmetric synthesis and dynamic resolution are discussed using transaminases. Protein engineering by directed evolution as well as rational design of transaminases under process condition is presented to develop efficient bioprocesses. 

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