Eine neue Familie von Lipoglycopeptid-Antibiotika mit einzigartigen strukturellen Merkmalen und ausgeprägter Aktivität gegen Gram-positive Bakterien wird von Stanislav S. Terekhov, Zakhar O. Shenkarev, Vladimir A. Korshun et al. in ihrem Forschungsartikel vorgestellt (DOI: 10.1002/ange.202104528). Gausemycine sind intrinsisch fluoreszierende Verbindungen mit einem einzigartigen Modus der antibakteriellen Wirkung. Die Analyse des Biosynthese-Genclusters entschlüsselte eine ungewöhnliche Enzymologie, die an der Bildung einer bisher unbekannten nicht-proteinogenen Aminosäure beteiligt ist.

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 com-pounds are cyclic peptides with a unique peptide core and several remarkable structural features, including unusual posi-tions 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 or-nithine 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. Gausemycins exhibit only slight Ca2+-dependence of an-timicrobial activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.