Recent Advances in Cyclodipeptide Synthases-Dependent Biosynthetic Pathway

Abstract

Diketopiperazines (DKPs) are derivatives of cyclodipeptides resulted from the condensation of two α-amino acids. The conformationally constrained six-membered ring makes DKP an attractive pharmacophore in medicinal chemistry, exhibiting a wide range of bioactivities. Recently, there has been increased interests in synthesizing DKPs and biosynthesis is an effective pathway to broaden their structural diversity. Different from non-ribosomal peptide synthetases (NRPSs)-dependent pathways, cyclodipeptide synthases (CDPSs) use aminoacyl-tRNAs (aa-tRNAs) as substrates and the resulting cyclodipeptides are further modified by associated tailoring enzymes to yield the final products. To date, six CDPS-dependent pathways for synthesizing DKPs compounds have been reported. A brief overview of recent progresses on CDPS-dependent DKPs biosynthetic pathway is provided.