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Gausemycin.pdf (4.72 MB)

Gausemycins A,B – Cyclic Lipoglycopeptides from Streptomyces Sp.

preprint
submitted on 28.09.2020 and posted on 30.09.2020 by Anton Tyurin, Vera Alferova, Alexander Paramonov, Maxim Shuvalov, Gulnara Kudryakova, Eugene Rogozhin, Alexander Zherebker, Vladimir Brylev, Alexey Chistov, Anna Baranova, Mikhail Biryukov, Igor Ivanov, Igor Prokhorenko, Natalia Grammatikova, Tatyana Kravchenko, Elena Isakova, Elena Mirchink, Elena Gladkikh, Elena Svirshchevskaya, Andrey Mardanov, Aleksey Beletsky, Milita Kocharovskaya, Valeriya Kulyaeva, Alexander Shashkov, Dmitry Tsvetkov, Nikolay Nifantiev, Alexander Apt, Konstantin Majorov, Svetlana Efimova, Nikolai Ravin, Evgeny Nikolaev, Olga Ostroumova, Genrikh Katrukha, Olda Lapchinskaya, Olga Dontsova, Stanislav Terekhov, Ilya Osterman, Zakhar Shenkarev, Vladimir Korshun
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.

Funding

RFBR 20-33-70215

RSF 19-74-30014

RFBR 19-14-00306

History

Email Address of Submitting Author

v-korshun@yandex.ru

Institution

Gause Institute of New Antibiotics

Country

Russia

ORCID For Submitting Author

0000-0001-9436-6561

Declaration of Conflict of Interest

none

Exports