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 - Funding Information:
This research was supported in part by budget funding of the topic “Isolation and Physico‐chemical Characterization of Microbially Produced Antibiotic Compounds” at the Gause Institute of New Antibiotics and by RFBR (project N 20‐33‐70215). NMR studies were supported by the RSF (project N 19‐74‐30014). Genome sequencing and mechanistic studies were supported in part by the RFBR (project No. 20‐54‐53014). The FTICR MS study was supported by the RSF (project No. 21‐47‐04405). The work of A.V.M., A.V.B. and N.V.R. was supported by the Ministry of Science and Higher Education of Russia. o o
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 -