Exploring the Substrate Flexibility of GrsB Thioesterase Leads to the Structural Reassignment of a Gramicidin S Variant.

ABSTRACT: Gramicidin S (GS) is a cyclic decapeptide derived from two pentapeptides. The C-terminal thioesterase (TE) domain of gramicidin S synthetase B (GrsB) dimerizes precursor pentapeptides and cyclizes the resulting linear decapeptide. Recently, a GS variant (GS-SA), in which a single D-Phe is replaced by L-Ser(Allyl), is reported via precursor-directed biosynthesis in a native GS producer. To understand how GrsB-TE processes such modified precursors, its substrate specificity using synthetic linear peptides is investigated. GrsB-TE cyclizes a substrate containing L-Ser(Allyl) at position 6 but not at position 1. However, the enzymatically synthesized GS-SA shows a different high-performance liquid chromatography retention time than that of the reported GS variant. Further structural and functi

SUBMITTER: Konno S 

PROVIDER: S-EPMC12630999 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature