Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.**

Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.** Full article

Journal

Angewandte Chemie International Edition
ISSN: 1433-7851 , E-ISSN: 1521-3773

Output data

Year: 2021, Volume: 60, Number: 34, Pages: 18694-18703 Pages count : 10 DOI: 10.1002/anie.202104528

Authors

Tyurin Anton P ¹ , Alferova Vera A ^1,2 , Paramonov Alexander S ² , Shuvalov Maxim V ^1,3 , Kudryakova Gulnara K ¹ , Rogozhin Eugene A ^1,2 , Zherebker Alexander Y ⁴ , Brylev Vladimir A ² , Chistov Alexey A ² , Baranova Anna A ^1,2 , Biryukov Mikhail V ^1,5 , Ivanov Igor A ² , Prokhorenko Igor A ^1,2 , Grammatikova Natalia E ¹ , Kravchenko Tatyana V ^1,2 , Isakova Elena B ¹ , Mirchink Elena P ¹ , Gladkikh Elena G ¹ , Svirshchevskaya Elena V ² , Mardanov Andrey V ⁶ , Beletsky Aleksey V ⁶ , Kocharovskaya Milita V ¹⁰ , Kulyaeva Valeriya V ¹ , Shashkov Alexander S ⁷ , Tsvetkov Dmitry E ⁷ , Nifantiev Nikolay E ⁷ , Apt Alexander S ⁸ , Majorov Konstantin B ⁸ , Efimova Svetlana S ⁹ , Ravin Nikolai V ⁶ , Nikolaev Evgeny N ⁴ , Ostroumova Olga S ⁹ , Katrukha Genrikh S ¹ , Lapchinskaya Olda A ¹ , Dontsova Olga A ^3,4 , Terekhov Stanislav S ^2,3 , Osterman Ilya A ⁴ , Shenkarev Zakhar O ¹⁰ , Korshun Vladimir A ^1,2

Affiliations

1	Gause Institute of New Antibiotics, B. Pirogovskaya 11, 119021, Moscow, Russia.
2	Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry RAS, Miklukho-Maklaya 16/10, 117997 Moscow, Russia
3	Department of Chemistry Lomonosov Moscow State University Leninskie Gory 1–3 119992 Moscow Russia
4	Skolkovo Institute of Science and Technology, Nobel Street 3, Skolkovo, 143026, Moscow Region, Russia.
5	Department of Biology Lomonosov Moscow State University Leninskie Gory 1–3 119992 Moscow Russia
6	Institute of Bioengineering Research Center of Biotechnology of the Russian Academy of Sciences Leninsky Prospect 33-2 119071 Moscow Russia
7	Zelinsky Institute of Organic Chemistry RAS, Leninsky Prospect 47, 119991, Moscow, Russia.
8	Central Tuberculosis Research Institute, Yauzskaya Alley 2, 107564, Moscow, Russia.
9	Institute of Cytology RAS, Tikhoretsky Prospect 4, 194064, St. Petersburg, Russia.
10	Moscow Institute of Physics and Technology, Institutsky Lane 9, Dolgoprydny, 141700 Moscow region, Russia

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.

Tyurin A.P. , Alferova V.A. , Paramonov A.S. , Shuvalov M.V. , Kudryakova G.K. , Rogozhin E.A. , Zherebker A.Y. , Brylev V.A. , Chistov A.A. , Baranova A.A. , Biryukov M.V. , Ivanov I.A. , Prokhorenko I.A. , Grammatikova N.E. , Kravchenko T.V. , Isakova E.B. , Mirchink E.P. , Gladkikh E.G. , Svirshchevskaya E.V. , Mardanov A.V. , Beletsky A.V. , Kocharovskaya M.V. , Kulyaeva V.V. , Shashkov A.S. , Tsvetkov D.E. , Nifantiev N.E. , Apt A.S. , Majorov K.B. , Efimova S.S. , Ravin N.V. , Nikolaev E.N. , Ostroumova O.S. , Katrukha G.S. , Lapchinskaya O.A. , Dontsova O.A. , Terekhov S.S. , Osterman I.A. , Shenkarev Z.O. , Korshun V.A.
Gausemycins A,B: Cyclic Lipoglycopeptides fromStreptomycessp.**
Angewandte Chemie International Edition. 2021. V.60. N34. P.18694-18703. DOI: 10.1002/anie.202104528 WOS Scopus OpenAlex

≡ Web of science:	WOS:000664203200001
≡ Scopus:	2-s2.0-85108500569
≡ OpenAlex:	W3161708973