Biocatalysis in reaction mixtures with undissolved solid substrates and products

Enzymatic synthesis in reaction mixtures with mainly undissolved substrates and/or products is a synthetic strategy in which the compounds are present mostly as pure solids. It retains the main advantages of conventional enzymatic synthesis such as high regio- and stereoselectivity, absence of racemisation and reduced side-chain protection. The reaction yields are improved and the necessity to use organic solvents to shift the thermodynamic equilibrium toward synthesis is reduced by product precipitation, which makes the synthesis favourable even in water. The thermodynamics of these reaction systems have been investigated in the last few years, resulting in methods to predict the direction of a typical reaction a priori. Furthermore, studies on kinetics, enzyme concentration, pH/temperature effects, mixing and solvent selection have opened new perspectives for the understanding, modelling, optimisation and the possible large scale application of such a strategy. In this review we have tried to cover most of the literature published in the last five to ten years on biocatalysis in substrate suspensions, focusing especially on cases where the reaction products precipitate