Biocatalysis industrial applications

In the enzyme design approach, as discussed in the first part of this chapter, one attempts to utilize the mechanistic understanding of chemical reactions and enzyme structure to create a new catalyst. This approach represents a largely academic research field aiming at fundamental understanding of biocatalysis. Indeed, the invention of functional artificial enzymes can be considered to be the ultimate test for any theory on enzyme mechanisms. Most artificial enzymes, to date, do not fulfill the conditions of catalytic efficiency and price per unit necessary for industrial applications. 

Much activity is evident in the application of enzymes in synthetic and natural products chemistry (9-26). Surprisingly, this is not a new field of endeavor, but rather one that was extensively developed for application in solving synthetic chemical problems in the steroid field. The earliest work in this field took place during the early twentieth century, and serious industrial application of biocatalysis began in the late 1940s (8). The successes obtained in steroid chemistry clearly underlined the potential for biocatalysis to contribute in other areas of natural products chemistry including that with the alkaloids. 

Roberts, N. J., Lye, G. J. Application of room temperature ionic liquids in biocatalysis Opportunities and challenges. In Ionic Liquids Industrial Applications for Green Chemistry, Rogers, R. D., Sheldon, K. R. Eds., American Chemical Society Washington, D.C., 2002, Vol. ACS Symposium Series 818. 

Biocatalysis covers a broad range of scientific and technical disciplines, which are geared to develop biocatalysts and biocatalytic processes for practical purposes. The natural pool of biocatalysts is extremely diverse and includes whole cells of microbial, plant or animal origin, as well as cell-free extracts and enz3rmes derived from these sources. The wide range of catalytic power offered by nature remains, however, largely imexplored. Currently, only a very small fraction of the known biocatalysts are actually being applied on a commercial scale. For example, of the approximately 4,000 known enzymes, about 400 are available commercially, but only about 40 are actually used for industrial applications. 

INDUSTRIAL APPLICATIONS OF WHOLE-CELL BASED BIOCATALYSIS... 

Whole-cell based biocatalysis utilizes an entire microorganism for the production of the desired product. One of the oldest examples for industrial applications of whole-cell biocatalysis is the production of acetic acid from ethanol with an immobilized Acetobacter strain, which was developed nearly 200 yr ago. The key advantage of whole-cell biocatalysis is the ability to use cheap and abundant raw materials and catalyze multistep reactions. Recent advances in metabolic engineering have brought a renaissance to whole-cell biocatalysis. In the following sections, two novel industrial processes that utilize whole-cell biocatalysis are discussed with emphasis on the important role played by metabolic engineering. 

Replacing Chemical Steps by Biotransformations Industrial Application and Processes Using Biocatalysis... 

Since the late 1960s immobilized biocatalysts have been extensively studied and used for the industrial production of important intermediates and products such as amino acids, sugars, lipids, acids, and pharmaceuticals [ 1-3]. A recent OECD report not only states that biocatalysts can and should be used in a wide range of industrial applications, but also identifies a need for reusable systems [4]. Improving the robustness of biocatalysts was also an important topic of a 1999 workshop of 50 leading scientific and industry experts in biocatalysis [5]. 

Industrial application of immobilized biocatalysts. Marcel Dekker, New York, pp 15-24 Schaffeld G, Bruzzone P, Illanes A et al. (1989) Enzymatic treatment of stickwater from fishmeal industry with the protease from Cucurbita ficifolia. Biotechnol Lett ll(7) 521-522 Schmedding DIM, van Gestel MJMC (2002) Enzymes in brewing. In Whitehurst RJ, Law BA (eds). Enzymes in food technology. CRC Press, Boca Raton, USA, pp 57-75 Schmid A, Dordick IS, Hauer B et al. (2(X)1) Industrial biocatalysis today and tomorrow. Nature 409 258-268... 

We have been investigating the production of value-added products from soybean oil. A Japanese patent application by Soda et al. (2) claimed the production of ricinoleic acid from oleic acid by Bacillus pumilus. Our initial goal was to produce ricinoleic acid from oleic acid by biocatalysis and hence to reduce the dependency on imported castor oil. Although we could not demonstrate the production of ricinoleic acid from oleic acid as did other investigators, including Soda s own group (2), our efforts led to discoveries of many new hydroxy fatty acids. These new products have potential industrial applications. Microbial oxidation of unsaturated fatty acids was reviewed recently (3). 

Ionic liquids are still in the research phase. Therefore, there are only a few industrial applications known (Fig. 20.3). However, there is a large field of potentially interesting applications (Table 20.3). Several pilots or industrial processes using ILs were publicly announced. There are few reviews which describe those applications in detail [1]. Most of the potential applications are as solvents or catalysts in many chemical reactions such as Diels-Alder, Friedel-Crafts reactions, and biocatalysis. Applications in other fields such as in separations, fluid applications, and analytical applications, are lower in numbers. There are now many companies who supply ionic liquids in gram scale to multi-ton scale. Some of the key suppliers are listed in Table 20.4. In this chapter, maiifly the applications in the pilot-plant and industrial phase will be discussed. Aspects of ionic liquid stability, cost, recycling, and waste disposal will be also discussed at the end of this chapter. 

Aki, T Kawamoto, S Shigeta, S Ono, K Hou, CT. Fatty acid-modifying enzymes implications for industrial applications, in houct, editor. Handbook ofindustrial biocatalysis, CRC Press 2005, 1-11. 

P450 biocatalysts operate - like any enzyme applied for industrial biocatalysis - under ambient conditions, thereby often exhibiting exquisite substrate specificity as well as regio- and/or stereoselectivity. Compared with other biocatalysts, however, P450s potentially have additional advantages for industrial applications ... 

Excellent and thorough books and reviews have been devoted to the use of biocatalysis in stereoselective synthesis, with focus on industrial applications, chiral intermediates, and green processes, and can be referred to for additional examples [56-63]. 

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