Scale‐up of enzymatic solid‐to‐solid peptide synthesis and enzyme recovery

The feasibility of scale‐up for applicutions of enzymatic solid‐to‐solid synthesis of dipeptides Was investigated by using Thermouse catalyzed synthesis of Z‐Asp‐Phe‐OMe as a model reaction. The reaction system involves typically only 10% (w/w) enzyme syspension added to dry solid substrates. Enzymatic solid‐to solid biocatalysis combines the main advantages of aqueous media, high catalytic acitivity, low water media, and high yields. A flow sheet for the whole process is described, as well as the use of a jacketed reactor with an anchor stirrer for various steps of the process, including the neutralization reaction to adjust the acid‐base condition of the reaction mixture. A solution for enzyme recycling, an important issue for scale‐up applications, is also suggested.