CONTINUOUS-PROCESSES WITH SOLUBLE ENZYMES

This paper surveys the use of continuously operating enzyme-membrane reactors with enforced flow where the retention of soluble enzymes in the reaction vessel is achieved by means of an ultrafiltration membrane. This technique has been commercialized in the acylase process for the synthesis of L-amino acids on a 200 ton/year level. It is especially useful for the application of multi-enzyme systems with cofactor regeneration. The synthesis Of L-tert-leucine from the corresponding alpha-keto acid has been achieved on a kilogram scale. Coenzymes coupled to water soluble polymers are retained in the membrane-reactor together with the enzymes. Use of suitable conditions prevents loss of enzyme and coenzyme by passage through the membrane or by deactivation. Therefore the costs of enzymes and coenzymes are no longer limitations for economic processes. In the continuously operating enzyme-membrane reactor regeneration of the coenzyme up to 600000 times was achieved. In continuous peptide synthesis space-time yields of 25 kg/(1 d) were obtained. To suppress side reactions very high catalyst concentrations are possible, yielding residence times below 4 min.