Putative tailoring enzymes that modify the initially assembled CDPscaffold can be found in almost all NRPS and CDPS gene clusters, and are responsible for installing functional groups crucial for the biological activities of CDPs.
The structures, reactions, medicinal chemical properties and potential therapeutic applications of 2,5-DKPs, particularly that with the interesting biological activities have previously been reviewed [,].
The smallest cyclic peptides built from amino acids are the so-called diketopiperazines (DKP). In recent research, the DKPs and higher functionalized analogs – the thiodiketopiperazines (TDKP) – have become attractive due to their broad biological activity (390). The DKP or TDKP moiety can be found in a great variety of mycotoxins. Both DKPs and TDKPs can, for example, be isolated from Aspergillus, Candida, Chaetomium, Gliocladium, Penicillium, and Verticillium species (7, 390). The most common structural motifs A–D of this class of compounds are depicted in Fig. 10.1. Many of these natural products show C 2 symmetry, which means they consist of two identical amino acids (R = R′ in Fig. 10.1).
NRPSs rely not only on the 20 canonical amino acids, but also use several different building blocks, including non-proteinogenic amino acids, and this contributes to the structural diversity of non-ribosomal peptides and their differential biological activities .
However, 2,5-DKPs belong to a relatively unexplored category of the bioactive cyclic peptides that may hold a great promise for the potential medicinal use in the future.
The increasing numbers of naturally occurring bioactive 2,5-DKPs have been obtained from various marine organisms, and the studies on these 2,5-DKPs have been the focus of many recent studies because of their potent biological activities.