Sergiev Laboratory

Start date – January 2017

Main focus of the group is identification and analysis of antibiotics acting on the ribosome. The group of P. Sergiev created a reporter strain of E.coli that contains two sensors of antibiotic action. The red fluorescent protein gene is induced upon DNA damage, caused by antibiotics, such as fluoroquinolones. The far red fluorescent protein gene Katushka2S is induced if cells are treated with inhibitors of protein biosynthesis. The system is well suited for high throughput screening of new antibiotics with the immediate recognition of the molecular target of antibiotic action. Application of this system allowed us to study mechanism of action of several antibiotics.

Work in collaboration with K. Severinov laboratory (Skoltech) and Yury Polikanov laboratory (University of Illinois) lead us to identification of new peptide antibiotic with unusual binding mode. This antibiotic, klebsazolicin binds peptide tunnel in a folded conformation, blocking progression of the nascent peptide.

Our laboratory is also focused on the modification of ribosomal RNA in a range of species. We are working on identification of putative methyltransferase genes that act on rRNA. These enzymes modulate translation and are essential for proper function of several gene expression control mechanisms.

Supervisor: Petr Sergiev

• Oligoglutamylation of E. coli ribosomal protein S6 is under growth phase control. Pletnev P, Nesterchuk M, Rubtsova M, Serebryakova M, Dmitrieva K, Osterman I, Bogdanov A, Sergiev P. Biochimie. 01.12.2019; 167:61-67. doi: 10.1016/j.biochi.2019.09.008.

• Mouse Trmt2B protein is a dual specific mitochondrial metyltransferase responsible for m⁵U formation in both tRNA and rRNA. Laptev I, Shvetsova E, Levitskii S, Serebryakova M, Rubtsova M, Bogdanov A Kamenski P, Sergiev P Dontsova O. RNA Biol. 27.10.2019; 1-10. doi: 10.1080/15476286.2019.1694733.

• Exploitation of Potentially New Antibiotics from Mangrove Actinobacteria in Maowei Sea by Combination of Multiple Discovery Strategies. Lu Q, Ye J, Huang Y, Liu D, Liu L, Dong K, Razumova E, Osterman I, Sergiev P, Dontsova O, Jia S, Huang D, Sun C. Antibiotics (Basel). 27.11.2019; 8(4). pii: E236. doi: 10.3390/antibiotics8040236.

• 2-Pyrazol-1-yl-thiazole derivatives as novel highly potent antibacterials. Ivanenkov Y, Yamidanov R, Osterman I, Sergiev P, Aladinskiy V, Aladinskaya A, Terentiev V, Veselov M, Ayginin A, Skvortsov D, Komarova K, Sadovnikov S, Matniyazov R, Sofronova A, Malyshev A, Machulkin A, Petrov R, Lukianov D, Iarovenko S, Bezrukov D, Baymiev A, Dontsova O; J Antibiot (Tokyo). 01.11.2019; 72(11):827-833. doi: 10.1038/s41429-019-0211-y.

• Identification of Novel Antibacterials Using Machine Learning Techniques. Ivanenkov Y, Zhavoronkov A, Yamidanov R, Osterman I, Sergiev P, Aladinskiy V, Aladinskaya A, Terentiev V, Veselov M, Ayginin A, Kartsev V, Skvortsov D, Chemeris A, Baimiev A, Sofronova A, Malyshev A, Filkov G, Bezrukov D, Zagribelnyy B, Putin E, Puchinina M, Dontsova O. Front Pharmacol. 08.2019;10:913. doi: 10.3389/fphar.2019.00913.

• Studies on Antibacterial Activity and Diversity of Cultivable Actinobacteria Isolated from Mangrove Soil in Futian and Maoweihai of China.Li F, Liu S, Lu Q, Zheng H, Osterman I, Lukyanov D, Sergiev P, Dontsova O, Liu S, Ye J, Huang D, Sun C. Evid Based Complement Alternat Med. 09.06.2019; 2019:3476567. doi: 10.1155/2019/3476567. eCollection 2019.

• Identification of pyrrolo-pyridine derivatives as novel class of antibacterials.Veselov M, Ivanenkov Y, Yamidanov R, Osterman I, Sergiev P, Aladinskiy V, Aladinskaya A, Terentiev V, Ayginin A, Skvortsov D, Komarova K, Chemeris A, Baimiev A, Sofronova A, Machulkin A, Petrov R, Maklakova S, Bezrukov D, Filkov G, Zainullina L, Maximova M, Zileeva Z, Kartsev V, Vakhitova Y, Dontsova O Mol Divers.04.2019. doi: 10.1007/s11030-019-09946-3.

• Structure of dirithromycin bound to the bacterial ribosome suggests new ways for rational improvement of macrolides.Khabibullina N, Tereshchenkov A, Komarova E, Syroegin E, Shiriaev D, Paleskava A, Kartsev V, Bogdanov A, Konevega A, Dontsova O, Sergiev P, Osterman I, Polikanov Y, Antimicrob Agents Chemother. 01.04.2019 pii: AAC.02266-18. doi: 10.1128/AAC.02266-18.

• LINC00116codes for a mitochondrial peptide linking respiration and lipid metabolism. Chugunova A, Loseva E, Mazin P, Mitina A, Navalayeu T, Bilan D, Vishnyakova P, Marey M, Golovina A, Serebryakova M, Pletnev P, Rubtsova M, Mair W, Vanyushkina A, Khaitovich P, Belousov V, Vysokikh M, Sergiev P, Dontsova O. Proc Natl Acad Sci U S A. 22.02.2019;116(11):4940-4945. doi: 10.1073/pnas.1809105116. Epub 2019 Feb 22.

• Nybomycin-producing Streptomyces isolated from carpenter ant Camponotus vagus.Zakalyukina Y, Birykov M, Lukianov D, Shiriaev D, Komarova E, Skvortsov D, Kostyukevich Y, Tashlitsky V, Polshakov V, Nikolaev E, Sergiev P, Osterman I.  21.02.2019;160:93-99. doi: 10.1016/j.biochi.2019.02.010.

• Structural and evolutionary insights into ribosomal RNA methylation. Sergiev P, Aleksashin N, Chugunova A, Polikanov Y, Dontsova O. Nat Chem Biol. 2018 Feb 14;14(3):226-235. doi: 10.1038/nchembio.2569. Review.PMID:29443970

• Escherichia coli ItaT is a type II toxin that inhibits translation by acetylating isoleucyl-tRNAIle. Wilcox B, Osterman I, Serebryakova M, Lukyanov D, Komarova E, Gollan B, Morozova N, Wolf YI, Makarova KS, Helaine S, Sergiev P, Dubiley S, Borukhov S, Severinov K Nucleic Acids Res. 2018 Jun 21. doi: 10.1093/nar/gky560.

• NMR assignments of the WBSCR27 protein related to Williams-Beuren syndrome.  Mariasina S, Petrova O, Osterman I, Sergeeva O, Efimov S, Klochkov V, Sergiev P, Dontsova O, Huang T, Chang C, Polshakov V.Biomol NMR Assign. 2018 Jun 4. doi: 10.1007/s12104-018-9827-2.

• Diversity, Novelty, and Antimicrobial Activity of Endophytic Actinobacteria From Mangrove Plants in Beilun Estuary National Nature Reserve of Guangxi, China. Jiang Z, Tuo L, Huang D, Osterman I, Tyurin A, Liu S, Lukyanov D, Sergiev P, Dontsova O, Korshun V, Li F, Sun C. Front Microbiol. 2018 May 4;9:868. doi: 10.3389/fmicb.2018.00868. eCollection 2018.

• Possible Role of Escherichia coli Protein YbgI. Sergeeva O, Bredikhin D, Nesterchuk M, Serebryakova M, Sergiev P, Dontsova O. Biochemistry (Mosc). 2018 Mar;83(3):270-280. doi: 10.1134/S0006297918030070.

• Mining for Small Translated ORFs. Chugunova A, Navalayeu T, Dontsova O, Sergiev P. J Proteome Res. 2018 Jan 5;17(1):1-11. doi: 10.1021/acs.jproteome.7b00707. Epub 2017 Dec 11.PMID:29188713

• 2-Guanidino-quinazolines as a novel class of translation inhibitors. Komarova Andreyanova E, Osterman I, Pletnev P, Ivanenkov Y, Majouga A, Bogdanov A, Sergiev P.Biochimie. 2017 Feb;133:45-55. doi: 10.1016/j.biochi.2016.11.008. Epub 2016 Dec 21.

• Klebsazolicin inhibits 70S ribosome by obstructing the peptide exit tunnel. Metelev M, Osterman I, Ghilarov D, Khabibullina N, Yakimov A, Shabalin K, Utkina I, Travin D, Komarova E, Serebryakova M, Artamonova T, Khodorkovskii M, Konevega A, Sergiev P, Severinov K, Polikanov Y. Nat Chem Biol. 2017 Aug 28. doi: 10.1038/nchembio.2462. PMID: 28846667

• Madumycin II inhibits peptide bond formation by forcing the peptidyl transferase center into an inactive state. Osterman I, Khabibullina N, Komarova E, Kasatsky P, Kartsev V, Bogdanov A, Dontsova O, Konevega A, Sergiev P, Polikanov Y, Nucleic Acids Res. 2017, 45, 12, 7507-7514.

• Application of sorting and next generation sequencing to study 5-UTR influence on translation efficiency in Escherichia coli. Evfratov S, Osterman I, Komarova E,  Pogorelskaya A, Rubtsova M,  Zatsepin T, Semashko T, Kostryukova E,  Mironov A, Burnaev E,  Krymova E, Gelfand M,  Govorun V, Bogdanov A, Sergiev P, Dontsova O. Nucleic Acids Res., 2017, 45, 3487-3502

• Sorting Out Antibiotics’ Mechanisms of Action: a Double Fluorescent Protein Reporter for High-Throughput Screening of Ribosome and DNA Biosynthesis Inhibitors. Osterman I, Komarova E, Shiryaev D, Korniltsev I, Khven I, Lukyanov D, Tashlitsky V, Serebryakova M, Efremenkova O, Ivanenkov Y, Bogdanov A, Sergiev P, Dontsova O. Antimicrob Agents Chemother. 2016, 60:7481-7489