Rational generation of lasso peptides based on biosynthetic gene mutations and site-selective chemical modifications.

ABSTRACT: Lasso peptides are a unique family of natural products whose structures feature a specific threaded fold, which confers these peptides the resistance to thermal and proteolytic degradation. This stability gives lasso peptides excellent pharmacokinetic properties, which together with their diverse reported bioactivities have garnered extensive attention because of their drug development potential. Notably, the threaded fold has proven quite inaccessible by chemical synthesis, which has hindered efficient generation of structurally diverse lasso peptides. We herein report the discovery of a new lasso peptide stlassin (1) by gene activation based on a Streptomyces heterologous expression system. Site-directed mutagenesis on the precursor peptide-encoding gene is carried out syst

SUBMITTER: Liu T 

PROVIDER: S-EPMC8480316 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature