Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp

Autor: Alexander S. Shashkov, Elena P. Mirchink, Olga S. Ostroumova, Valeriya V. Kulyaeva, Mikhail V. Biryukov, Genrikh S. Katrukha, Dmitry S. Tsvetkov, Andrey V. Mardanov, Vera A. Alferova, Anna A. Baranova, Evgeny N. Nikolaev, Nikolai V. Ravin, Tatyana V. Kravchenko, Alexander S. Apt, Alexey A. Chistov, Natalia E. Grammatikova, Vladimir A. Brylev, Elena B. Isakova, Ilya A. Osterman, Maxim V. Shuvalov, Anton P. Tyurin, S. S. Terekhov, Gulnara K. Kudryakova, A. V. Beletsky, Vladimir A. Korshun, Olda A. Lapchinskaya, Eugene A. Rogozhin, Nikolay E. Nifantiev, Milita V Kocharovskaya, Olga A. Dontsova, Alexander Zherebker, Igor A. Prokhorenko, Svetlana S. Efimova, Igor Ivanov, Elena G. Gladkikh, Konstantin B. Majorov, Zakhar O. Shenkarev, Alexander S. Paramonov, Elena V. Svirshchevskaya
Rok vydání: 2020
Předmět:
Popis: 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.
Databáze: OpenAIRE