Uses of Biocatalysis

The earliest industrial application of biocatalysts began without a scientific foundation in 1874 Christian Hansen founded the first biocatalysts company, which 

Epoxide hydrolases Resolution of aryl and substituted alicyclic epoxides. Enantioselective catalyst 

Monooxygenases, oxidizing enzymes Oxidation, Baeyer—ViUiger oxidation 

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The use of biocatalysis in the manufacture of APIs can address some of the 12 principles of green chemistry set out by Anastas and Wamer. ° For example, biocatalytic processes can ... 

Thus the use and practice of biocatalysis at full scale has waxed and waned over the years. In the past, one factor limiting the use of biocatalysis has been the availability of a variety of enzymes and the time taken to refine/evolve enzymes for specific industrial apphcations. Hydrolytic enzymes such as lipases and proteases designed for other industrial uses such as detergents and food processing have always been available in bulk, and indeed used by process chemists. 

It is clear from the examples in this book that the use of biocatalysis can produce some very cost-effective and environmentally acceptable processes, and the authors anticipate that the use of this technology will increase as synthetic organic chemists realize its value and begin to look for strategic disconnections in the synthetic sequence of new target molecules where a biocatalytic step can be applied to utmost benefit. Thus, biocatalysis should be seen as a routine part of the synthetic toolbox and, in some cases, the reagent of choice for transformations such as the reduction of ketones to chiral alcohols, and not as a technology of last resort when all else has failed. 

The use of biocatalysis for the production of chemicals started to receive serious interest in the 1960s with the development of immobilized aminoacylases for the production of chirally pure amino acids by Tanabe Seigaku of Japan, as well as the application of penicillin acylase for the production of 6-aminopenicillanic acid (6-APA), a key... 

Chiral Pharmaceutical Intermediates. The use of biocatalysis for producing chirally pure pharmaceuticals is now an accepted technology that complements alternative chemical and physical methods.23 The size of the current world market for single enantiomer drugs, over 150 billion in 2002, offers plenty of incentive to develop competitive biocatalytic routes for key intermediates. The market for chiral intermediates themselves, although far smaller, is still considerable at over 7 billion... 

The increasing use of biocatalysis in research and industrial production, especially in the developing field of chirotechnology, is foreseeable. Advances in the following areas seem most promising. 

Numerous authors have given overviews over biotransformations used in industry13-11. A very recent monograph summarizes almost 100 processes including many details on reaction conditions, screening of the biocatalyst or the product application 21. The use of biocatalysis from the viewpoint of a chemist in the laboratory is also summarized in several books. Recent ones are 12-14. ... 

In recent years, the industrial use of biocatalysis has been reviewed several times [1-3, 23], Also, since the first reports [17, 24] on biocatalysis in ILs appeared in 2000 this field has often been reviewed, recently for example by the groups of Sheldon [14,21], Kragl [6], and Kazlauskas [7]. Comprehensive tables of the various enzymatic reactions attempted in ILs can be found in these excellent reviews (see, for example. Ref. [6]). Here only general trends will be outlined and illustrated by selected examples. 

This use of biocatalysis may come as a surprise to a generation of chemists and biologists who are struggling to accommodate a new technology called biotransformations . It is pertinent now to rephrase the question posed at... 

The processes for amino acid production can be roughly divided into enzymatic, extractive, chemical, and fermentative methods. Most amino acids were initially obtained by extractive methods from protein-rich resources. The main problems with this method are product purity, satisfying the demand for the amino acid, the availability of the raw materials, and environmental concerns about the process as odor or waste treatment can be an issue. Chemical processes are also not predominant (except for glycine and d,l-methionine), primarily due to the high costs of the optical resolution to generate L-forms from the racemic mixtures. The use of biocatalysis, for example, for production of L-cysteine is mainly limited by the cost of the substrates used. Fermentation is the most applied method for commercial production of L-amino acids, and is also used for production of L-lysine. 

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]. 

The use of biocatalysis for synthetic chemistry is significantly important for reducing the environmental footprint of chentical processes. The possibility of setting up a cascade of enzyme-catalyzed reactions in the same pot is very attractive. In nature, many biochemical transformations are achieved through a combination of several different proteins [65]. For example, the enzymes in mitochondria were settled on the surface of a compartment, in its interior, in its membrane or in any combination of these for the citric acid-catalyzed cycle. Van Dongen et al. mimicked this method to design one porous polymersome to anchor enzymes at three different locations in their lumen (glucose oxidase, GO ), in their bilayer membrane Candida antarctica lipase B, CalB), and on their surface (horseradish peroxidase, HRP). As shown in Scheme 8.22, a mixture of block... 

Znabet, A., et al., A highly efficient synthesis of telaprevir by strategic use of biocatalysis and multicomponent reactions. Chem. Commun., 2010.46(42) 7918-7920. 

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