Enzymatic synthesis with mainly undissolved substrates at very high concentrations

This review describes a recently developed method for enzymatic synthesis with mainly undissolved substrates at very high concentrations. At the end of the reaction, up to 80% (w/w) reaction mixture is product, a fact which is promising in terms of industrial applications and large-scale systems. In comparison with other approaches for enzymatic peptide synthesis, this method gives a very high mass of product combined with good reaction yields and rates. We will analyze the historical development from two different directions which have been reported; these are described with terms like "solid-to-solid conversion" and "heterogenous eutectic mixtures". The reaction requires and takes place in a liquid phase which, however may be of very small volume. This review analyzes in detail the function of additional water or organic solvents (around 10% w/w). The liquid phase formed is usually dependent on these third components; however, it can also result from a eutectic two-substrate mixture, We summarize what is known so far about the thermodynamics and kinetics. Finally, the possibility for and main problems of scale up are discussed. (C) 1998 Elsevier Science Inc.