Biochemical studies on cyclophane-forming enzymes in peptide natural product biosynthesis

Cyclophane-containing peptides are important in drug discovery, with several examples used clinically. Plants, fungi, and bacteria have emerged as rich sources of such chemotype containing a single aromatic ring. These peptide natural products are biosynthesized ribosomally and posttranslationally modified.

We identified a suite of radical SAM/SPASM modifying enzymes that catalyze the formation of C(sp2)-C(sp3) crosslink on three-residue motifs creating a rigid cyclophane. This transformation defines a new family of peptide natural products termed triceptides. In this talk, we will delve deeper into the potential of cyclophane-forming enzymes as versatile biocatalysts for generating diverse peptide cyclophanes.