Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp.*.
Anton P TyurinVera A AlferovaAlexander S ParamonovMaxim V ShuvalovGulnara K KudryakovaEugene A RogozhinAlexander Ya ZherebkerVladimir A BrylevAlexey A ChistovAnna A BaranovaMikhail V BiryukovIgor A IvanovIgor A ProkhorenkoNatalia E GrammatikovaTatyana V KravchenkoElena B IsakovaElena P MirchinkElena G GladkikhElena V SvirshchevskayaAndrey V MardanovAleksey V BeletskyMilita V KocharovskayaValeriya V KulyaevaAlexander S ShashkovDmitry E TsvetkovNikolay E NifantievAlexander S AptKonstantin B MajorovSvetlana S EfimovaNikolai V RavinEvgeny N NikolaevOlga S OstroumovaGenrikh S KatrukhaOlda A LapchinskayaOlga A DontsovaStanislav S TerekhovIlya Andreevich OstermanZakhar O ShenkarevVladimir A KorshunPublished in: Angewandte Chemie (International ed. in English) (2021)
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), and N-acylation of the ornithine side chain. Gausemycins have pronounced activity against Gram-positive bacteria. Mechanistic studies highlight significant differences compared to known glyco- and lipopeptides. Gausemycins exhibit only slight Ca2+ -dependence of activity and induce no pore formation at low concentrations. Moreover, there is no detectable accumulation of cell wall biosynthesis precursors under treatment with gausemycins.