Premium
Gausemycins A,B: Cyclic Lipoglycopeptides from Streptomyces sp. **
Author(s) -
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.
Publication year - 2021
Publication title -
angewandte chemie international edition
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.831
H-Index - 550
eISSN - 1521-3773
pISSN - 1433-7851
DOI - 10.1002/anie.202104528
Subject(s) - stereochemistry , cyclic peptide , streptomyces , ornithine , chemistry , amino acid , peptide , biosynthesis , biochemistry , tyrosine , acylation , bacteria , biology , arginine , genetics , enzyme , catalysis
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 Ca 2+ ‐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 Ca 2+ ‐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.