Department of Biomolecular Chemistry

Department of Biomolecular Chemistry (headed by Ilia V. Yampolsky) was established in 2017.

Scientific focus of the Department is aimed to study the structural basis and chemical mechanisms of action of biologically active compounds using the examples of bioluminescence and antibiotics activity. The main feature of our research is to study biologically active compounds within the “complete cycle” from a molecule to a gene: isolation of low molecular components and their structure elucidation, synthesis of biologically active compounds and their functional analogues, investigation of mechanisms of their action, and, finally, isolation, purification, sequencing of proteins and cloning of genes, encoding them. So we investigate the mechanisms of functioning of biological molecules in a broad sense: biosynthesis of natural compounds (small molecules and proteins), chemical basis of their activity and work of genes and their regulation.


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Ilia Yampolsky

  • Russia, Moscow, Ul. Miklukho-Maklaya 16/10 — On the map
  • IBCh RAS, build. БОН, office. 525
  • Phone: +7(495)995-55-57#2007
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In Nature Biotechnology, scientists from IBCh RAS have announced the feasibility of creating plants that produce their own visible luminescence. It was revealed that bioluminescence found in some mushrooms is metabolically similar to the natural processes common among plants. By inserting DNA obtained from the mushroom Neonothopanus nambi, the scientists were able to create plants that glow much brighter than previously possible. Plants containing the mushroom DNA glow continuously throughout their lifecycle, from seedling to maturity. This biological light can be used for observing the inner workings of plants. In contrast to other commonly used forms of bioluminescence, such as from fireflies, unique chemical reagents are not necessary for sustaining mushroom bioluminescence.


  1. Mitiouchkina T, Mishin AS, Somermeyer LG, Markina NM, Chepurnyh TV, Guglya EB, Karataeva TA, Palkina KA, Shakhova ES, Fakhranurova LI, Chekova SV, Tsarkova AS, Golubev YV, Negrebetsky VV, Dolgushin SA, Shalaev PV, Shlykov D, Melnik OA, Shipunova VO, Deyev SM, Bubyrev AI, Pushin AS, Choob VV, Dolgov SV, Kondrashov FA, Yampolsky IV, Sarkisyan KS (2020). Plants with genetically encoded autoluminescence. Nat Biotechnol 38 (8), 944–946

Among acid-sensitive ion channels (ASIC) the ASIC1a and ASIC3 subunits are the most attractive pharmacological targets. The inhibition of these channels by specific ligands can treat many socially significant diseases, such as chronic and pathological pain, ischemic stroke, and Parkinson's disease. Sevanol, a natural lignan isolated from Thymus armeniacus, inhibits the activity of ASIC1a and ASIC3 isoforms and has a significant analgesic and anti-inflammatory effect. However its production by chemical synthesis is a labor and material consumption process from many stages. The structure-functional investigation  allowed to minimize the structure of Sevanol and to keep both analgesic activity in animal models, and ASICs inhibitory effect for analogs. The location of Sevanols binding site in the Central vestibule of ASIC1a was predicted in mathematical modeling experiment and its competition with the FRRF-amide peptide for this binding site was proved by electrophysiology. Sevanols analogues had a significant analgesic and anti-inflammatory effect in animal models by various administration routes- intravenous or intramuscular (parenteral methods), as well as intranasal or oral (non-invasive methods). Cozy synthesis method developed for each analogs allow us to recommend these molecules as potential prodrugs, since the absence of side effects identified at this moment together with oral activity are potent competitive advantages of new molecules to existent analgesic drugs. The results were published in Pharmaceuticals (Basel) journal.

Created by: Osmanov D.I., Vladimirov A.A., Koshelev S.G., Andreev, Y.A., Kozlov S.A. from laboratory of neuroreceptors and neuroregulators, Belozerova, O.A., Kublitski V.S. from laboratory of metabolic pathways chemistry, Chugunov A.O., Efremov R.G. from laboratory of biomolecular modeling, Palikov V.A., Palikova, Y.A., Shaikhutdinova E.R., Dyachenko I.A. from laboratory of biological examination, and  Gvozd A.N. from scientific center of biomedical technologies of the Federal medical-biological Agency.

The researchers from Yampolsky lab have successfully characterized three key low-molecular-weight components of Odontosyllis undecimdonta bioluminescence system: luciferin,  oxyluciferin (Green) and a nonspecific luciferin oxidation product (Pink). These compounds were revealed to be highly unusual tricyclic heterocycles containing three sulfur atoms in different electronic states. Together the structures of these low-molecular-weight components of Odontosyllis bioluminescent system have enabled us to propose chemical transformation pathways for the enzymatic (luminescent) and non-enzymatic (dark) oxidation of luciferin. Moreover Odontosyllis oxyluciferin was established to be the only green primary emitter described for any known bioluminescent marine organism.


  1. Kotlobay AA, Dubinnyi MA, Purtov KV, Guglya EB, Rodionova NS, Petushkov VN, Bolt YV, Kublitski VS, Kaskova ZM, Ziganshin RH, Nelyubina YV, Dorovatovskii PV, Eliseev IE, Branchini BR, Bourenkov G, Ivanov IA, Oba Y, Yampolsky IV, Tsarkova AS (2019). Bioluminescence chemistry of fireworm Odontosyllis. Proc Natl Acad Sci U S A 116 (38), 18911–18916

Scientists uncovered a mechanism of fungal luminescence and created luminescent yeasts

Group of synthetic biology,  Laboratory of Chemistry of Metabolic Pathways

Scientists from the Institute of Bioorganic Chemistry in Moscow and Krasnoyarsk Federal Research Center together with their Russian and foreign colleagues have fully described the mechanism of fungal luminescence. They found that fungi utilize only four key enzymes to produce light and that transfer of these enzymes into any other organisms makes them bioluminescent. To illustrate this, the authors have created a luminescent yeast strain visible to the naked eye. The theoretical and experimental parts of the study were supported by Russian Science Foundation. The results of the study are published in the journal Proceedings of the National Academy of Sciences.

Decoding of the mechanism of fungal luminescence become possible because of preceding research in this field. Back in the early 19th century, it was discovered that it was mycelium that made rotten trees glow. In 2009, Anderson G. Oliveira and Cassius V. Stevani, co-authors of the present paper, determined that a single biochemical mechanism is shared by all fungi emitting light. In 2015–2017, a team of Russian scientists led by Ilia Yampolsky made a series of key discoveries. In particular, the team determined the structure of luciferin, the molecule that emits light when oxidized.


  1. Kotlobay AA, Sarkisyan KS, Mokrushina YA, Marcet-Houben M, Serebrovskaya EO, Markina NM, Gonzalez Somermeyer L, Gorokhovatsky AY, Vvedensky A, Purtov KV, Petushkov VN, Rodionova NS, Chepurnyh TV, Fakhranurova LI, Guglya EB, Ziganshin R, Tsarkova AS, Kaskova ZM, Shender V, Abakumov M, Abakumova TO, Povolotskaya IS, Eroshkin FM, Zaraisky AG, Mishin AS, Dolgov SV, Mitiouchkina TY, Kopantzev EP, Waldenmaier HE, Oliveira AG, Oba Y, Barsova E, Bogdanova EA, Gabaldón T, Stevani CV, Lukyanov S, Smirnov IV, Gitelson JI, Kondrashov FA, Yampolsky IV (2018). Genetically encodable bioluminescent system from fungi. Proc Natl Acad Sci U S A 115 (50), 12728–12732

We developed a new method of target protein labeling called Protein-PAINT. This method is based on reversible binding of a protein domain with a fluorogenic dye that leads to a strong increase in fluorescence intensity. Using computer molecular docking we engineered three mutants of bacterial lipocalin Blc with different affinities to the fluorogen. It was shown that the fluorogen enters live cell quickly and stains target proteins fused with the Blc mutants. The new method ensures an order of magnitude higher photostability of the fluorescence signal in comparison with fluorescent proteins. Protein-PAINT also enables prolonged super-resolution fluorescence microscopy of living cells in both single molecule detection and stimulated emission depletion regimes.

Synthesis of the core structure of fungal terpenoid Panal - a component of bioluminescent fungus Panellus stipticus

Laboratory of Chemistry of Metabolic Pathways

The structure of panal, an earlier presumed fungal luciferin precursor, was determined in 1988 by Nakamura and colleagues [Nakamura H, Kishi Y, Shimomura O. Tetrahedron 1988, 44, 1597]. Panal is a cadalane-type bicyclic sesquiterpenoid, total synthesis of which was carried out using the Diels-Alder cycloaddition, followed by Barbier and metathesis reactions.


  1. Baranov MS, Kaskova ZM, Gritсenko R, Postikova SG, Ivashkin PE, Kislukhin AA, Moskvin DI, Mineev KS, Arseniev AS, Labas YA, Yampolsky IV (2017). Synthesis of Panal Terpenoid Core. Synlett 28 (5), 583–588

Mechanism of Fungal Bioluminescence study

Laboratory of Chemistry of Metabolic Pathways

The structure of fungal oxyluciferin was determined for the first time. A unique mechanism of bioluminescence, consisting of carbon dioxide cleavage through retro-[4 + 2]cycloaddition was proposed. Conclusions are supported by theoretical and experimental analysis, including the synthesis of the [18O]-labeled endoperoxide of the native luciferin. A number of artificial fungal luciferins with varying  bioluminescence spectra were obtained.


  1. Kaskova ZM, Dörr FA, Petushkov VN, Purtov KV, Tsarkova AS, Rodionova NS, Mineev KS, Guglya EB, Kotlobay A, Baleeva NS, Baranov MS, Arseniev AS, Gitelson JI, Lukyanov S, Suzuki Y, Kanie S, Pinto E, Mascio PD, Waldenmaier HE, Pereira TA, Carvalho RP, Oliveira AG, Oba Y, Bastos EL, Stevani CV, Yampolsky IV (2017). Mechanism and color modulation of fungal bioluminescence. Sci Adv 3 (4), e1602847
  2. Tsarkova AS, Kaskova ZM, Yampolsky IV (2016). A Tale of Two Luciferins: Fungal and Earthworm New Bioluminescent Systems. Acc Chem Res 49 (11), 2372–2380
  3. Kaskova ZM, Tsarkova AS, Yampolsky IV (2016). 1001 lights: Luciferins, luciferases, their mechanisms of action and applications in chemical analysis, biology and medicine. Chem Soc Rev 45 (21), 6048–6077

Deep structure-functional analysis of amino acid substitutions on photophysical properties of green fluorescent proteins

Group of synthetic biology,  Laboratory of genetically encoded molecular tools

A so called “fitness landscape” was for the first time experimentally probed at the whole protein level using GFP as a model. A unique approach developed in this work enabled to correlate a function (fluorescence) with amino acid sequence of several tens of thousands of random mutants, revealing a number of negative and positive epistatic interactions between substitutions. Characterization of the GFP fitness landscape allows for computer prediction of properties of new mutants of fluorescent proteins. It also has important implications for several fields including molecular evolution and protein design.

Using calculations of the possible electron transfer pathways from excited GFP chromophore to external molecules and further experimental verification of these hypotheses, we constructed mutants with blocked electron transfer pathway and correspondingly increased photostability. This strategy may represent a new approach toward enhancing photostability of fluorescent proteins.


Figure. (A) Scheme of GFP fitness landscape derived from analysis of 51000 mutants. The GFP sequence arranged in a circle, each column representing one amino acid site. In the first circle, the colour intensity of the squares indicates the brightness of a single mutation at the corresponding site relative to the wild type, shown in the centre. Sites with positive and negative epistatic interactions between pairs of mutations are connected by green and black lines, respectively. In circles further away from the centre, representing genotypes with multiple mutations, the fraction of the column coloured green (black) represents the fraction of genotypes corresponding to high (low) fluorescence among all assayed genotypes with a mutation at that site. (B) Electron transfer in GFP. Upper panel – scheme of calculated pathway of electron transfer from the chromophore to external acceptor molecule via tyrosine-145 as an intermediate electron acceptor. Bottom panel – photobleaching curves of EGFP and its mutants in the presence of oxidant in the medium, showing a dramatic enhancement of photostability due to blocking the electron transfer pathway. 


  1. Sarkisyan KS, Bolotin DA, Meer MV, Usmanova DR, Mishin AS, Sharonov GV, Ivankov DN, Bozhanova NG, Baranov MS, Soylemez O, Bogatyreva NS, Vlasov PK, Egorov ES, Logacheva MD, Kondrashov AS, Chudakov DM, Putintseva EV, Mamedov IZ, Tawfik DS, Lukyanov KA, Kondrashov FA (2016). Local fitness landscape of the green fluorescent protein. Nature 533 (7603), 397–401
  2. Bogdanov AM, Acharya A, Titelmayer AV, Mamontova AV, Bravaya KB, Kolomeisky AB, Lukyanov KA, Krylov AI (2016). Turning on and off Photoinduced Electron Transfer in Fluorescent Proteins by π-Stacking, Halide Binding, and Tyr145 Mutations. J Am Chem Soc 138 (14), 4807–4817
  3. Acharya A, Bogdanov AM, Grigorenko BL, Bravaya KB, Nemukhin AV, Lukyanov KA, Krylov AI (2017). Photoinduced chemistry in fluorescent proteins: Curse or blessing? Chem Rev 117 (2), 758–795

The mechanism of bioluminescence of siberian worm Fridericia heliota was studied

Laboratory of Chemistry of Metabolic Pathways

Structure of Fridericia oxyluciferin was elucidated: oxyluciferin is a product of oxidative decarboxylation of luciferin from Fridericia heliota in the presence of luciferase. The mechanism of Fridericia bioluminescencewas studied: it includes the step of activating the carboxyl group of lysine via formation of an adenylate intermediate, cyclization to oxetanone and it's decay to the excited oxyluciferin molecule.

The structure of a key bioluminescent substrate of higher fungi was elucidated

Laboratory of Chemistry of Metabolic Pathways

For the first time the structure of fungal luciferin was identified. Also the mechanism of it's biosynthesis via hydroxylation of secondary fungal metabolite hispidin by NADPH-dependent enzyme was determined. Luciferin (3-hydroxyhispidin) is a substrate of the enzyme luciferase in a bioluminescence reaction. The structures of the luciferin and it's precursor were proven by methods of NMR spectroscopy and mass spectrometry. It is shown that the luciferin is a common bioluminescent substrate for a number of higher fungi.


  1. Purtov KV, Petushkov VN, Baranov MS, Mineev KS, Rodionova NS, Kaskova ZM, Tsarkova AS, Petunin AI, Bondar VS, Rodicheva EK, Medvedeva SE, Oba Y, Oba Y, Arseniev AS, Lukyanov S, Gitelson JI, Yampolsky IV (2015). The Chemical Basis of Fungal Bioluminescence. Angew Chem Int Ed Engl 54 (28), 8124–8128