Macrocyclizing-thioesterases in bacterial non-ribosomal peptide biosynthesis

Abstract

Macrocyclization of peptides reduces conformational flexibilities, potentially leading to improved drug-like properties. However, side reactions such as epimerization and oligomerization often pose synthetic challenges. Peptide-cyclizing biocatalysts in the biosynthesis of non-ribosomal peptides (NRPs) have remarkable potentials as chemoenzymatic tools to facilitate more straightforward access to complex macrocycles. This review highlights the biocatalytic potentials of NRP cyclases, especially those of cis-acting thioesterases, the most general cyclizing machinery in NRP biosynthesis. Growing insights into penicillin-binding protein-type thioesterases, a relatively new group of trans-acting thioesterases, are also summarized.

Graphical abstract