Abstract
We report a novel family of natural lipoglycopeptides produced by Streptomyces sp. INA-Ac-5812. Two major
components of the mixture, named gausemycins A and B, were isolated, and their structures were elucidated. The compounds are
cyclic peptides with a unique peptide core and several remarkable structural features, including unusual positions of D-amino acids,
lack of the Ca2+
-binding Asp-X-Asp-Gly (DXDG) motif, tyrosine glycosylation with arabinose, presence of 2-amino-4-hydroxy-4-
phenylbutyric acid (Ahpb) and chlorinated kynurenine (ClKyn), N-acylation of the ornithine side chain. These major components
of the peptide antibiotic family have pronounced activity against Gram-positive bacteria. The mechanism of action of gausemycins
was explored by a number of methods, showing significant differences compared to glycopeptides and related lipopeptides. For
example, gausemycins exhibit no Ca2+
-dependence of antimicrobial activity and induce no pore formation at low concentrations.
Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.