Fig. 3.

Sactipeptide RiPP natural products synthesized by commensal gut microbes contain metalloenzyme-installed thioether linkages. (a) Structures of sactipeptides produced by human-associated bacteria [PDB accession codes: subtilosin A, 1PXQ; thurincin H, 2LBZ; thuricin CD, 2L9X and 2LA0]. Leader sequences are shown in blue and brackets indicate thioether linkages. (b) Mechanistic proposals for thioether bond formation invoking an iron–sulfur cluster activated thiol (radical scheme) or a ketoimine intermediate (polar scheme). (c) The CteB (PDB accession code: 5WGG) active site depicting one of the SPASM domain auxiliary clusters located in close proximity to the SAM substrate bound to the radical SAM cluster.