Peptide macrocyclization: The reductase of the nostocyclopeptide synthetase triggers the self-assembly of a macrocyclic imine

Experiments were conducted, which show that a C-terminal reductase domain of the respective nostocyclopeptide (ncp) nonribosomal peptides (NRPs) catalyzes the reductive release of the mature peptide chain from the synthetase and thereby triggers the spontaneous formation of the imino head-to-tail linkage. The experiments also provided proof that the ncp molecular self-assembly is based on the intrinsic conformation of the linear heptapeptide aldehyde and strongly depends on the nature of the C- and N-terminal amino acids.