Accessing Diverse Pyridine-Based Macrocyclic Peptides by a Two-Site Recognition Pathway.

ABSTRACT: Macrocyclic peptides are sought-after molecular scaffolds for drug discovery, and new methods to access diverse libraries are of increasing interest. Here, we report the enzymatic synthesis of pyridine-based macrocyclic peptides (pyritides) from linear precursor peptides. Pyritides are a recently described class of ribosomally synthesized and post-translationally modified peptides (RiPPs) and are related to the long-known thiopeptide natural products. RiPP precursors typically contain an N-terminal leader region that is physically engaged by the biosynthetic proteins that catalyze modification of the C-terminal core region of the precursor peptide. We demonstrate that pyritide-forming enzymes recognize both the leader region and a C-terminal tripeptide motif, with each contributing to site

SUBMITTER: Nguyen DT 

PROVIDER: S-EPMC9247985 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature