Indolylamide Macrocyclization by a ThiF-like Enzyme Family Member.

ThiF-like enzymes are present in diverse RiPP biosynthetic pathways and are known to catalyze reactions such as thiolactone and phosphoramidate bond formation. To uncover new chemical space for ThiF-like enzymes, we utilized a global genome mining approach and identified a minimal RiPP cluster in the human pathogen . In vitro characterization of IndF demonstrated the first indolylamide (Trp-Ile) linkage in a RiPP pathway and a new reaction type catalyzed by a ThiF-like enzyme.