The feasibility of scale-up for applications of enzymatic solid-to-solid sy
nthesis of dipeptides was investigated by using Thermoase catalyzed synthes
is of Z-Asp-Phe-OMe as a model reaction. The reaction system involves typic
ally only 10% (w/w) enzyme suspension added to dry solid substrates. Enzyma
tic solid-to-solid biocatalysis combines the main advantages of aqueous med
ia, high catalytic activity, low water media, and high yields. A flow sheet
for the whole process is described, as well as the use of a jacketed react
or with an anchor stirrer for various steps of the process, including the n
eutralization reaction to adjust the acid-base condition of the reaction mi
xture. A solution for enzyme recycling, an important issue for scale-up app
lications, is also suggested.