Fig. 1. Schematic representation of peptide bond formation as performed by a NRPS extension module containing an epimerisation domain. Amino acid selection and subsequent activation are performed by the adenylation (A)-domain (first panel, starting from the left), after which the amino acid is transferred onto the PPant moiety of the neighbouring carrier protein (CP) domain. Following this, the aminoacyl-CP then acts as the acceptor in peptide bond formation performed by the upstream condensation domain (second panel). At this point, the peptide present on the upstream donor CP is transferred onto the acceptor aminoacyl-CP, extending the peptide by one residue. Depending on the stereochemistry required at the C-terminal position of the peptide, an epimerisation domain can alter the standard l-configuration into the non-natural d-form (third panel). The stereochemical state of the peptide is then assessed by the downstream C-domain, where the peptidyl-CP now acts as the donor substrate for the next round of peptide bond formation (fourth panel).