TY - JOUR
T1 - Gausemycins A,B
T2 - Cyclic Lipoglycopeptides from Streptomyces sp.**
AU - Tyurin, Anton P.
AU - Alferova, Vera A.
AU - Paramonov, Alexander S.
AU - Shuvalov, Maxim V.
AU - Kudryakova, Gulnara K.
AU - Rogozhin, Eugene A.
AU - Zherebker, Alexander Y.
AU - Brylev, Vladimir A.
AU - Chistov, Alexey A.
AU - Baranova, Anna A.
AU - Biryukov, Mikhail V.
AU - Ivanov, Igor A.
AU - Prokhorenko, Igor A.
AU - Grammatikova, Natalia E.
AU - Kravchenko, Tatyana V.
AU - Isakova, Elena B.
AU - Mirchink, Elena P.
AU - Gladkikh, Elena G.
AU - Svirshchevskaya, Elena V.
AU - Mardanov, Andrey V.
AU - Beletsky, Aleksey V.
AU - Kocharovskaya, Milita V.
AU - Kulyaeva, Valeriya V.
AU - Shashkov, Alexander S.
AU - Tsvetkov, Dmitry E.
AU - Nifantiev, Nikolay E.
AU - Apt, Alexander S.
AU - Majorov, Konstantin B.
AU - Efimova, Svetlana S.
AU - Ravin, Nikolai V.
AU - Nikolaev, Evgeny N.
AU - Ostroumova, Olga S.
AU - Katrukha, Genrikh S.
AU - Lapchinskaya, Olda A.
AU - Dontsova, Olga A.
AU - Terekhov, Stanislav S.
AU - Osterman, Ilya A.
AU - Shenkarev, Zakhar O.
AU - Korshun, Vladimir A.
N1 - Publisher Copyright:
© 2021 Wiley-VCH GmbH.
PY - 2021/8/16
Y1 - 2021/8/16
N2 - 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.
AB - 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.
KW - antibacterial activity
KW - antibiotics
KW - biosynthesis
KW - lipoglycopeptides
KW - structure elucidation
UR - http://www.scopus.com/inward/record.url?scp=85108500569&partnerID=8YFLogxK
U2 - 10.1002/anie.202104528
DO - 10.1002/anie.202104528
M3 - Article
C2 - 34009717
AN - SCOPUS:85108500569
SN - 1433-7851
VL - 60
SP - 18694
EP - 18703
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
IS - 34
ER -