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

Abstract

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.