Biocatalysis catalysts

Substrate synthesis, reaction parameters, enantioenrichment via biocatalysis, catalyst handling, economic considerations Catalyst screening, substrate design, process optimization, application of Josiphos ligands, ligand synthesis, scale-up Production considerations, comparison with classical methods... 

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. 

Biocatalysis refers to catalysis by enzymes. The enzyme may be introduced into the reaction in a purified isolated form or as a whole-cell micro-organism. Enzymes are highly complex proteins, typically made up of 100 to 400 amino acid units. The catalytic properties of an enzyme depend on the actual sequence of amino acids, which also determines its three-dimensional structure. In this respect the location of cysteine groups is particularly important since these form stable disulfide linkages, which hold the structure in place. This three-dimensional structure, whilst not directly involved in the catalysis, plays an important role by holding the active site or sites on the enzyme in the correct orientation to act as a catalyst. Some important aspects of enzyme catalysis, relevant to green chemistry, are summarized in Table 4.3. 

Applications of sol-gel-processed interphase catalysts. Chemical Reviews, 102, 3543-3578. Pierre, A.C. (2004) The sol-gel encapsulation of enzymes. Biocatalysis and Biotransformation, 22, 145-170. Shchipunov, Yu.A. (2003) Sol-gel derived biomaterials of silica and carrageenans. Journal of Colloid and Interface Science, 268, 68-76. Shchipunov Yu.A. and Karpenko T.Yu. (2004) Hybrid polysaccharide-silica nanocomposites prepared by the sol-gel technique. Langmuir, 20, 3882-3887. 

For a while, in the early 1990s, the interest in the use of enzymes in organic synthesis increased at an almost exponential rate and two-volume works were needed even to summarize developments in the field151. Now, at the turn of the century, it is abundantly clear that the science of biotransformations has a significant role to play in the area of preparative chemistry however, it is, by no stretch of the imagination, a panacea for the synthetic organic chemist. Nevertheless, biocatalysis is the method of choice for the preparation of some classes of optically active materials. In other cases the employment of man-made catalysts is preferred. In this review, a comparison will be made of the different methods available for the preparation of various classes of chiral compounds161. 

In each of these areas the relative merits of biocatalysis versus other catalytic methodologies will be assessed. Note that the text is given an asterisk ( ) when mention is made of a catalyst for a reduction or oxidation reaction that is featured in the later experimental section of this book. 

In summary, the formation of optically active compounds through hydrolysis reactions is dominated by biocatalysis mainly due to the availability and ease of use of a wide variety of esterases, lipases and (to a lesser extent) acylases. Epoxide ring-opening (and related reactions) is likely to be dominated by salen-metal catalysts while enzyme-catalysed nitrile hydrolysis seems destined to remain under-exploited until nitrilases or nitrile hydratases become commercially available. 

So, in the final analysis, biocatalysis should not be considered in a separate sector available only to the specialist bioorganic chemist. It is one method, in the portfolio of catalytic techniques, that is available to all chemists for the solution of present and future problems in organic synthesis. To erect a Chinese wall between the natural and non-natural catalysts is totally illogical and prevents some creative thinking, particularly in the area of coupled natural/ non-natural catalysts11611 and biomimetic systems11621. 

A detailed review of the literature of non-enzymic catalysts is given in Comprehensive Asymmetric Catalysis eds Jacobsen, E.N., Pfaltz, A. and Yamamoto, H. Springer-Verlag, Berlin/Heidelberg, 1999. As an introductory text for post-graduate students see Catalysis in Asymmetric Synthesis, Williams, J.MJ. Sheffield Academic Press, Sheffield, UK, 1999. A comparison of biocatalysis versus chemical catalysis has also been made by Averill, B.A., Laane, N.W.M., Straathof, A.JJ. and Tramper, J., in Catalysis An Integrated Approach (eds van Santen, R.A. van Leeuwen, P.W.N.M., Moulijn, J.A. and Averill, B.A.) Elsevier, The Netherlands, 1999, Chapter 7. 

Perhaps less clear to a newcomer to a particular area of chemistry is when to use biocatalysis as a key step in a synthesis, and when it is better to use one of the alternative non-natural catalysts that may be available. Therefore we set out to extend the objective of Preparative Biotransformations, so as to cover the whole panoply of catalytic methods available to the synthetic chemist, incorporating biocatalytic procedures where appropriate. 

This chapter will consider some of the most interesting of current approaches to the evolution of enzyme mimics, in the context of continuing dramatic progress in protein and nucleotide engineering. There are excellent practical as well as intellectual reasons for the broad interest in this topic. Catalysis is a major preoccupation of the chemical industry if the application of the principles of biocatalysis can lead to robust and efficient catalysts tailor-made for reactions of economic importance the area will become even more a focus of intense activity and investment. 

Membranes can be used as a matrix for immobilization of a catalyst. Four basic types of catalysts are relevant (a) enzymes and (b) whole cells for biocatalysis (c) oxides and (d) metals for nonbiological synthesis. Biocatalysts will be considered first since their immobilization in (or on) the membrane was explored much earlier. Five techniques have been studied in varying degrees. They are (1) enzyme contained in the spongy fiber matrix ... 

Efficient biocatalysis in neat organic solvent depends on the careful choice of the method of dehydrated enzyme preparation and solvent used. Optimization of these factors towards a given transformation is often known as catalyst formulation and solvent, or medium, engineering respectively, both of which will be briefly discussed below. Catalyst engineering which also provides a powerful method of improving activity and stability, is discussed in Chapter 2. 

Because enzymes are insoluble in organic solvent, mass-transfer limitations apply as with any heterogeneous catalyst. Water-soluble enzymes (which represent the majority of enzymes currently used in biocatalysis) have hydrophilic surfaces and so tend to form aggregates or stick to reaction vessel walls rather than form the fine dispersions that are required for optimum efficiency. This can be overcome by enzyme immobilization, as discussed in Section 1.5. 

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