Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp.

• Published in: Angewandte Chemie Vol. 133; no. 34; pp. 18842 - 18851
• Main Authors: Tyurin, Anton P., Alferova, Vera A., Paramonov, Alexander S., Shuvalov, Maxim V., Kudryakova, Gulnara K., Rogozhin, Eugene A., Zherebker, Alexander Y., Brylev, Vladimir A., Chistov, Alexey A., Baranova, Anna A., Biryukov, Mikhail V., Ivanov, Igor A., Prokhorenko, Igor A., Grammatikova, Natalia E., Kravchenko, Tatyana V., Isakova, Elena B., Mirchink, Elena P., Gladkikh, Elena G., Svirshchevskaya, Elena V., Mardanov, Andrey V., Beletsky, Aleksey V., Kocharovskaya, Milita V., Kulyaeva, Valeriya V., Shashkov, Alexander S., Tsvetkov, Dmitry E., Nifantiev, Nikolay E., Apt, Alexander S., Majorov, Konstantin B., Efimova, Svetlana S., Ravin, Nikolai V., Nikolaev, Evgeny N., Ostroumova, Olga S., Katrukha, Genrikh S., Lapchinskaya, Olda A., Dontsova, Olga A., Terekhov, Stanislav S., Osterman, Ilya A., Shenkarev, Zakhar O., Korshun, Vladimir A.
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 16.08.2021
• Subjects: Acylation; Amino acids; antibacterial activity; antibiotics; Arabinose; Biosynthesis; Calcium; Calcium ions; Cell walls; Chemistry; Glycosylation; lipoglycopeptides; Lipopeptides; Low concentrations; Ornithine; Peptides; Phenylbutyric acid; Pore formation; Streptomyces; structure elucidation; Tyrosine
• ISSN: 0044-8249; 1521-3757
• DOI: 10.1002/ange.202104528

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. A family of natural lipoglycopeptides produced by actinobacteria and named gausemycins showed pronounced activity against Gram‐positive bacteria. Gausemycins have a unique peptide core that includes 2‐amino‐4‐hydroxy‐4‐phenylbutyric acid (Ahpb), chlorinated kynurenine (ClKyn), O‐arabinosylated tyrosine, and Nδ‐acylated ornithine residues (see structure). Mechanistic studies highlight significant differences to known antibiotics.