One-Pot Synthesis of Diverse dl -Configuration Dipeptides by a Streptomyces d -Stereospecific Amidohydrolase

Abstract

The synthesis of diverse DL-configuration dipeptides in a one-pot reaction was demonstrated by using a function of the aminolysis reaction of a D-stereospecific amidohydrolase from Streptomyces sp., a clan SE, S12 family peptidase categorized as a peptidase with D-stereospecificity. The enzyme was able to use various aminoacyl derivatives, including L-aminoacyl derivatives, as acyl donors and acceptors. Investigations of the specificity of the peptide synthetic activity revealed that the enzyme preferentially used D-aminoacyl derivatives as acyl donors. In contrast, L-amino acids and their derivatives were preferentially used as acyl acceptors. Consequently, the synthesized dipeptides had a DL-configuration when D- and L-aminoacyl derivatives were mixed in a one-pot reaction. This report also describes that the enzyme produced cyclo(D-Pro-L-Arg), a specific inhibitor of family 18 chitinase, with a conversion rate for D-Pro benzyl ester and L-Arg methyl ester to cyclo(D-Pro-L-Arg) of greater than 65%. Furthermore, based on results of cyclo(D-Pro-L-Arg) synthesis, we propose a reaction mechanism for cyclo(D-Pro-L-Arg) production.