Biocatalysis in Non-conventional Media: Medium Engineering Aspects

During the past decade much progress has been made in the fundamental understanding of the phenomena that govern biocatalysis in non-conventional media. The factors that affect biocatalytic reactions and the activity and stability of biocatalysts in these reaction media are generally associated with the crucial role of water and the need to keep biocatalysts in their active conformation. For the rational design of biocatalytic processes in the reaction media, discussed in this review, some basic rules have been formulated. These rules may serve as useful tools for future optimization of biocatalysis in nonconventional media and for engineering media for synthetic purposes. INTRODUCTION Integration of biotransformation steps in synthetic chemistry is gaining much scientific as well as industrial interest (Laane et al., 1987a, Tramper et al., 1992). The specificity and selectivity of biocatalysts make them very attractive as possible catalysts for reactions which are difficult and/or expensive to carry out by chemical means. For a long time applications of biotransformations in synthetic routes have been hampered by the general idea that biocatalysts (enzymes and whole cells) are only active in aqueous solutions and under mild conditions. Recently, it has become clear that biocatalysts are not so sensitive as expected. They can function under harsh conditions, such as extreme pH, temperatures and pressures, high salt concentrations, or in the presence of other additives (Monsan and Combes, 1984). They are also found to be active in all sorts of non-conventional media, such as organic solvents, aqueous two-phase systems, solid media, gases and supercritical fluids (Tramper et al., 1992). These findings drastically increase the applicability of biocatalysis in organic synthesis. In this review we will focus on the latest progress made in medium engineering and its effect on both activity and stability of the biocatalyst. Medium engineering not only involves the substitution of aqueous reaction media by non-conventional media, it also implies the adaptation of the microenvironment of the biocatalyst by immobilization or by introduction of additives for stabilization of the biocatalyst. The non-conventional media dealt with in this review are organic solvents and supercritical fluids. Other non-conventional media, which will not be discussed here, are aqueous twophase systems and solid and gaseous media. Aqueous two-phase systems are formed, when two solutions of water-soluble polymers or a concentrated salt solution and a polymer solution are mixed. The physical characteristics and the effects of phase components, pH, temperature etc., as well as several biotechnological applications of these systems have recently been reviewed by Andersson and Hahn-Hagerdal (1990) and King (1992). The latest advancements in biocatalysis in gaseous and solid media have recently been discussed by Robert et a2. (1992) and Lamare and Legoy (1993).