Synthesis and recovery of aspartame involving enzymatic deformylation step

Abstract

The invention relates to the synthesis of aspartame involving enzymatic deformylation of an N-formyl-α-L-aspartyl-L-phenylalanine compound by treatment with an enzyme having formylmethionyl peptide deformylase activity and having as a co-factor group 5 to 11 bivalent metal ions. The invention also relates to selective preparation and recovery of aspartame from a mixture of N-formyl-α- and β-L-aspartyl-L-phenylalanine compounds by treatment with such enzyme. And finally, the invention relates to one-pot enzymatic synthesis of aspartame from N-formyl-L-aspartic acid and L- or D,L-phenylalanine methyl ester involving an enzymatic deformylation reaction simultaneously with an enzymatic coupling reaction, as well as to one-pot di- or oligopeptide synthesis by simultaneous enzymatic coupling and deformylation reactions in general.

1 - 29 . (Canceled).  
     
     
         30 . Method for the synthesis of di-or oligopeptides or derivatives thereof from two starting materials, the first of which is an N-formyl protected amino acid which is capable of undergoing an enzymatic coupling reaction with a second amino acid or derivative thereof, or with a di-or oligo-peptide or derivative thereof, compound, wherein the N-formyl protecting group of the first starting material is retained during the enzymatic coupling reaction with the second starting material, whereby said protecting group is cleaved off enzymatically, using an enzyme having formylmethionyl peptide deformylase activity and having as a co-factor bivalent metal ions chosen from the group of group 5 to 11 metals from the periodic system of elements, from the reaction compound at a substantially higher, i. e. at least 10× higher, rate than from the first starting material, and wherein two enzymes are involved simultaneously for the enzymatic coupling reaction between the starting materials and the enzymatic deformylation of the reaction compound.