Leader-Independent C‑Terminal Modification by a Radical <i>S</i>‑Adenosyl‑l‑methionine Maturase Enables Macrocyclic GLP-1-Like Peptides.

ABSTRACT: Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a rapidly expanding family of natural products in which biosynthetic maturase enzymes tailor ribosomal precursors into bioactive products. Classical RiPP maturation relies on an N-terminal leader sequence in the precursor peptide and a complementary RiPP-recognition element in the enzyme to guide substrate binding. Herein, we interrogated PapB, a radical S-adenosyl-l-methionine RiPP maturase known to introduce thio-(seleno)-ether cross-links and discovered that its catalytic reach extends well beyond this paradigm. PapB efficiently processes substrates that lack any canonical leader sequence, demonstrating bona fide leader-independent activity. To highlight the practical value of this capability, w

SUBMITTER: Pedigo JK 

PROVIDER: S-EPMC12715619 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature