Non-ribosomal peptide cyclase-directed chemoenzymatic synthesis of lariat lipopeptides.

ABSTRACT: Lariat-shaped lipopeptides are important antimicrobial agents; however, their complex structures pose synthetic challenges that hamper efficient structural diversification. Here we report a new chemoenzymatic approach that facilitates access to lariat-shaped macrocycles. Unprotected, branched peptides bearing multiple nucleophiles, including a native amino terminus and a pseudo-amino terminus, were site-selectively cyclized using versatile non-ribosomal peptide cyclases, generating an array of lariat peptides with diverse sequences and ring sizes. The generality of this strategy was demonstrated using two penicillin-binding protein-type thioesterases, SurE and WolJ, as well as one type-I thioesterase, TycC thioesterase. Furthermore, the remaining nucleophile, which was not involved in the

SUBMITTER: Kobayashi M 

PROVIDER: S-EPMC12768971 | biostudies-literature | 2026 Jan

REPOSITORIES: biostudies-literature