Macrolactamization of glycosylated peptide thioesters by the thioesterase domain of tyrocidine synthetase

33Citations
Citations of this article
26Readers
Mendeley users who have this article in their library.

Abstract

The 35 kDa thioesterase (TE) domain excised from the megadalton tyrocidine synthetase (Tyc Syn) retains autonomous capacity to macrocyclize peptidyl thioesters to D-Phe 1-L-Leu 10-macrolactams. Since a number of nonribosomal peptides undergo O-glycosylation events during tailoring to gain biological activity, the Tyc Syn TE domain was evaluated for cyclization capacity with glycosylated peptidyl-S-NAC substrates. First, Tyr 7 was replaced with Tyr(β-D-Gal) and Tyr(β-D-Glc) as well as with Ser-containing β-linked D-Gal, D-Glc, D-GlcNAc, and D-GlcNH 2, and these new analogs were shown to be cyclized with comparable k cat/K m catalytic efficiency. Similarly, Gal- or tetra-O-acetyl-Gal-Ser could also be substituted at residues 5, 6, and 8 in the linear decapeptidyl-S-NAC sequences and cyclized without substantial loss in catalytic efficiency by Tyc Syn TE. The cyclic glycopeptides retained antibiotic activity as membrane perturbants in MIC assays, opening the possibility for library construction of cyclic glycopeptides by enzymatic macrocyclization.

Cite

CITATION STYLE

APA

Lin, H., Thayer, D. A., Wong, C. H., & Walsh, C. T. (2004). Macrolactamization of glycosylated peptide thioesters by the thioesterase domain of tyrocidine synthetase. Chemistry and Biology, 11(12), 1635–1642. https://doi.org/10.1016/j.chembiol.2004.09.015

Register to see more suggestions

Mendeley helps you to discover research relevant for your work.

Already have an account?

Save time finding and organizing research with Mendeley

Sign up for free