Core-peptide length steers atropopeptide cross-linking and an excision route to diketopiperazine alkaloids
Researchers at Goethe University Frankfurt in Germany and ETH Zurich in Switzerland reported in the Journal of the American Chemical Society, published online on 13 October, that core-peptide length, rather than sequence alone, can determine which cross-linking pattern an atropopeptide-forming cytochrome P450 installs.
Summary. Researchers at Goethe University Frankfurt in Germany and ETH Zurich in Switzerland reported in the Journal of the American Chemical Society, published online on 13 October, that core-peptide length, rather than sequence alone, can determine which cross-linking pattern an atropopeptide-forming cytochrome P450 installs. Atropopeptides are ribosomally synthesised and post-translationally modified peptides (RiPPs) that range from simple monocycles to polycyclic architectures built by multiple C–C and C–N cross-links from a single P450 enzyme. The study frames this as substrate-controlled catalysis in which precursor length steers complexity.
Research context (RUO). The authors further describe an unusual proteolytic excision of an internal amino acid in mature atropopeptides, generating species that spontaneously convert into pyrroloindoline-containing diketopiperazines and thereby connecting atropopeptides to DKP-derived alkaloid scaffolds. The paper is a biosynthetic and mechanistic chemistry study on purified enzymatic systems and characterised products. It does not report a clinical programme or any recommendation for use in people. For RiPP and natural-product laboratories, the contribution is a length-based design rule and an excision-linked scaffold hop documented with structural and activity context in the article itself.
