Biocatalysis engineering

Before discussing the medium engineering phenomenon and its synthetic relevance in details, it is useful to offer a brief overview of the fundamentals of biocatalysis in organic media. 

The aspects of medium engineering summarized so far were a hot topic in biocatalysis research during the 1980s and 1990s [5]. Nowadays, all of them constitute a well-established methodology that is successfully employed by chemists in synthetic applications, both in academia and industry. In turn, the main research interests of medium engineering have moved toward the use of ionic liquids as reaction media and the employment of additives. 

Some of the industrial biocatalysts are nitrile hydralase (Nitto Chemicals), which has a productivity of 50 g acrylamide per litre per hour penicillin G amidase (Smith Kline Beechem and others), which has a productivity of 1 - 2 tonnes 6-APA per kg of the immobilized enzyme glucose isomerase (Novo Nordisk, etc.), which has a productivity of 20 tonnes of high fmctose syrup per kg of immobilized enzyme (Cheetham, 1998). Wandrey et al. (2000) have given an account of industrial biocatalysis past, present, and future. It appears that more than 100 different biotransformations are carried out in industry. In the case of isolated enzymes the cost of enzyme is expected to drop due to an efficient production with genetically engineered microorganisms or higher cells. Rozzell (1999) has discussed myths and realities... 

However, the transfer of this technology from laboratory to industrial scale requires advances in the engineering of biocatalysis environment, particularly when one or more components are poorly water soluble [5-8]. 

In 1982, Lilly [21] reviewed the first two-liquid phase biocatalysis. In 1987 and 1992, Lilly s group [39,40] published reviews dealing with process engineering of biphasic bioreactors. In 1993, Van Sonsbeek et al. [41] gave an overview on biocatalysis in different biphasic... 

Kragl, 1J., Kruse, W., Hummel, W. and Wandrey, C. (1996) Enzyme engineering aspects of biocatalysis cofactor regeneration as example. Biotechnology and Bioengineering, 52, 309-319. 

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. 

There is huge potential in the combination of biocatalysis and electrochemistry through reaction engineering as the linker. An example is a continuous electrochemical enzyme membrane reactor that showed a total turnover number of 260 000 for the enantioselective peroxidase catalyzed oxidation of a thioether into its sulfone by in situ cathodic generated hydrogen peroxide - much higher than achieved by conventional methods [52],... 

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. 

Guo-Qiang Lin, Laboratory of Biocatalysis and Bioprocessing, State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, PR China... 

In vitro multi-enzyme systems are set up by the combination of enzyme modules including pathway and even pathway-unrelated enzymes. Also, the synthesis of saccharides in combination with de novo enzymatic sugar synthesis can be accomplished. This so-called combinatorial biocatalysis can be performed in sequential reactors or in a one-pot reaction vessel which challenges further reaction engineering for optimization. Even the combination of an enzyme module with a chemical... 

In summary, the combination of enzymes is advantageous from an enzymol-ogy and reachon engineering point of view. Reaction yields can be increased by avoiding product inhibition of single enzymatic reachons. Product decomposihon (e.g. by hydrolysis) can be overcome by further enzymatic transformahons. Tedious isolation of intermediate products is not necessary. However, both strategies - combinatorial biocatalysis and combinatorial biosynthesis - have their disadvantages. The in vitro approach needs every enzyme to be produced by recombinant techniques and purified in high amounts, which is in some cases difficult to achieve. On the other hand, product isolation from a biotransformation with permeabilized or whole host cells can be tedious and results in low yields. 

Laane, C. (1987) Medium-Engineering for Bio-Organic Synthesis. Biocatalysis, 1, 17-22. 

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