Active site remodelling of a cyclodipeptide synthase redefines substrate scope

Abstract

Cyclodipeptide synthases (CDPSs) generate a wide range of cyclic dipeptides using aminoacylated tRNAs as substrates, however the substrate selection mechanism is not yet known. Here, the authors investigate the substrate promiscuity of two histidine-incorporating CDPSs to generate an extensive library of products which complement the chemical realm of histidine-containing cyclic dipeptides.