Exploring the Substrate Flexibility of GrsB Thioesterase Leads to the Structural Reassignment of a Gramicidin S Variant
Sho Konno, Tomoe Mizuguchi, Atsuko Suzuki, Miyu Tanaka, Fumihiro Ishikawa, Akihiro Taguchi, Atsuhiko Taniguchi, Genzoh Tanabe, Yoshio Hayashi
TL;DR
Researchers found that a thioesterase enzyme can process modified building blocks to make a variant of gramicidin S, leading to a structural correction of the variant.
Contribution
The study reveals stereochemical flexibility in GrsB-TE and corrects the structure of a reported GS variant.
Findings
GrsB-TE can cyclize a substrate with L-Ser(Allyl) at position 6 but not at position 1.
The reported GS-variant actually contains D-Ser(Allyl) instead of L-Ser(Allyl).
Structural and functional analyses confirmed the stereochemical flexibility of GrsB-TE.
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 functional analyses, including 1H nuclear magnetic resonance, antimicrobial assays, and circular…
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Taxonomy
TopicsChemical Synthesis and Analysis · Biochemical and Structural Characterization · Carbohydrate Chemistry and Synthesis