Biocatalysis scope

Although the focus here is on the integration of biocatalysis with chemocataly-sis (bio-chemo cascades) for carbohydrates as renewable feedstocks, some representative examples (from laboratory to industrial scale) of both bio-bio and chemo-chemo cascades are also given below for comparison of their relative scope and limitations. 

Fig. 13.16 Merging reaction parameters of chemocatalysis (blank area) to that of biocatalysis (black area) to exploit fully the scope of bio-chemo cascade conversions.

The scope and limitations of biocatalysis in non-conventional media are described. First, different kinds of non-conventional reaction media, such as organic solvents, supercritical fluids, gaseous media and solvent-free systems, are treated. Second, enzyme preparations suitable for use in these media are described. In several cases the enzyme is present as a solid phase but there are methods to solubilise enzymes in non-conventional media, as well. Third, important reaction parameters for biocatalysis in non-conventional media are discussed. The water content is of large importance in all non-conventional systems. The effects of the reaction medinm on enzyme activity, stabihty and on reaction yield are described. Finally, a few applications are briefly presented. 

Gotfredsen, S.E., Ingvorsen, K., Yde, B. and Andersen, O. (1985) The scope of biocatalysis in organic chemical processing. In Biocatalysts in organic syntheses, edited by J.Trampereta/., pp. 3-18. Amsterdam Elsevier. 

Antibody Catalysis. Recent advances in biocatalysis have led to the generation of catalytic antibodies exhibiting aldolase activity by Lemer and Barbas. The antibody-catalyzed aldol addition reactions display remarkable enantioselectivity and substrate scope [18]. The requisite antibodies were produced through the process of reactive immunization wherein antibodies were raised against a [Tdiketone hapten. During the selection process, the presence of a suitably oriented lysine leads to the condensation of the -amine with the hapten. The formation of enaminone at the active site results in a molecular imprint that leads to the production of antibodies that function as aldol catalysts via a lysine-dependent class I aldolase mechanism (Eq. 8B2.12). 

In this chapter, we will focus on those bioorganic reactions in which biocatalysts, in particular, play a crucial role. We will not discuss peptide or natural product synthesis, as conventional organic chemistry will be covered by other chapters in this book. Also the discussion of the development of DN A chips, certainly one of the most exciting developments in the field of pTAS, is beyond the scope of this chapter, and the interested reader is referred to some excellent reviews [330,331], First, the application of bioorganic chemistry in diagnostics will be discussed. This will be followed by a discussion on biocatalysis in microreactors. Finally, the recent development of cells on a chip is highlighted. 

Enzymes are, for the most part, soluble in water and not obviously suited for use in organic solvents. Many enzymes are denatured by exposure to solvents, and still others require water as part of their catalytic action. Prior to 1980 there were several reports of biocatalysis in solvents, however, it was Alexander Klibanov and co-workers in the 1980s who first clearly demonstrated the potential of biocatalysis in organic media.17,18 The use of such media, typically organic solvents, has greatly expanded the scope of biocatalysis for several reasons ... 

During the last two decades tremendous progress has been made in the field of biocatalysis. This chapter is not intended as a comprehensive review, but rather a presentation of the scope, potential and limitations of the highly interdisciplinary approach of biocatalysis. 

Although enzymes are an important class of enantioselective catalysts, a systematic coverage of biocatalysis was beyond the scope of this work. However, the reader should be aware that biocatalysts can be an attractive alternative to synthetic chiral catalysts and in many chapters, references to related enzymatic transformations are given. An important new addition to biocatalysis are catalytic antibodies and their use for enantioselective transformations is summarized in chapter 40. 

The application of aqueous / supercritical biphasic media is not restricted to metal complex catalysis but has proven effective also for enzymatic and whole-cell biocatalysis [36]. In general, water plays an important role in coimection with biocatalysis. If water is completely absent, enzymes are often not catalytically active under supercritical conditions [37]. In the literature many examples of biocatalysis with supercritical fluids containing various amounts of water are known and a detailed account of this field is outside the scope of the present discussion. One example to highlight the use of a true biphasic system is the carboxylation of pyrrole... 

The oxidation of phenols to catechols or hydroquinones by tyrosinase enzymes has been developed for biocatalysis. For example, the ortho-hydroxylation of L-tyrosine 162 (and also substituted variants) to give l-DOPA 163 has been extensively studied due to the importance of l-DOPA in the treatment of Parkinson s disease [92, 93]. An arene hydroxy lating enzyme having a broad substrate scope is 2-hydroxybiphenyl 3-monooxygenase from Pseudomonas azelaica, which is able to oxidize many ortho-substituted phenols 68 to the corresponding catechols 127 [94], as shown in Scheme 32.19. A notable example of an industrial biocatalytic arene hydroxylation that has been employed on very large scale (lOOm fermentation) is the pora-hydroxylation of R)-2-phenoxypropionic acid 164 by whole cells of Beauveria bassiana Lu 700 to give (R)-2-(4-hydroxyphenoxy)propionic acid 165, an important intermediate in herbicide manufacture [95]. 

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