Fig. 8.

Postulated late-stage modification of the peptide in kistamicin biosynthesis. OxyA_kis and OxyC_kis are recruited to their NRPS-bound heptapeptide substrates by the X-domain present in the last module of the NRPS machinery. OxyC_kis introduces the first crosslink—the C-O-D ring, which is followed by OxyA_kis-catalysed insertion of the D-E ring that is only present in Type V GPAs. Based on the reactivity and promiscuity of the OxyC_kis enzyme, we then hypothesise that OxyC_kis acts to install the third crosslink, the expanded A-O-B crosslinking, before the completed kistamicin A is cleaved from the NRPS by the actions of the terminal thioesterase domain