Biocatalytic Tetrapeptide Macrocyclization by Cryptic Penicillin-binding Protein-type Thioesterases.

ABSTRACT: Cyclic tetrapeptides (CTPs) are a diverse class of natural products with a broad range of biological activities. However, they are extremely challenging to synthesize due to the ring strain associated with their small ring size. While chemical methods have been developed to access CTPs, they generally require the presence of certain amino acids, limiting their substrate scopes. Herein, we report the first bioinformatics guided discovery of a thioesterase from a cryptic biosynthetic gene cluster for peptide cyclization. Specifically, we hypothesized that predicted Penicillin-binding type thioesterases (PBP-TEs) from cryptic nonribosomal peptide synthetase gene clusters containing four adenylation domains would catalyze tetrapeptide cyclization. We found that one of the predicted PBP-TEs, WP

SUBMITTER: Jeannette PL 

PROVIDER: S-EPMC11601455 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature