Laboratory of Chemistry of Metabolic Pathways

Department of Biomolecular Chemistry

Head: Ilia Yampolsky, D.Sc
ivyamp@ibch.ru+7(499)724-84-77

yampolsky.ibch.ru/

bioluminescence, total synthesis, luciferin, luciferase, chromophores, medicinal chemistry

The Laboratory was established in 2017 on the basis of  the Total Synthesis Group which was created in the Laboratory of Molecular technologies at IBCH RAS, headed by Sergey Lukyanov. The mission of the group is to apply organic synthesis to solving actual problems in biochemistry, molecular biology and medicinal chemistry.

This includes:

  • structural design and synthesis of model compounds for studying biochemical processes
  • total synthesis of natural products
  • design, synthesis and testing of drug candidates
  • offering our expertise in organic synthesis to biological and biomedical researchers in collaborative projects

 

 

LATEST NEWS
 
Our Accounts of Chemical Research (ACS) cover with review of the latest developments in bioluminescent systems research of our group
 
CURRENT
 
  • Studies of fungal bioluminescence

Photograph by Professor Cassius Stevani (University of San Paulo, Brazil)

The Guardian about our work

  • Studying bioluminescence of marine worms Chaetopterus variopedatus

Photograph courtesy Dimitri Deheyn, Scripps Institution of Oceanography at UC San Diego

  • Studying Studying bioluminescence mechanism of Siberian earthworms Fridericia heliota

 
 
 
(А) Structure of Fridericia luciferin. (B) Bioluminescence of Fridericia heliota. The photograph is courtesy of Alexander Semenov (the White Sea Biological Station, Biology Department of Lomonosov Moscow State University). (C) Luminescence of synthetic Fridericia luciferin . (D) Comparison of in vivo bioluminescence spectra of worms, with in vitro bioluminescence spectra of natural and synthetic samples of luciferin.
 
  • Development of novel class of fluorescent dyes based on GFP chromophore
 
  • Development of anti-influenza drug candidates based on structural analogs of Flutimide

 

 
  • Enantioselective total synthesis of fungal terpenoid panal from bioluminescent fungus Panellus stipticus

 

 
Panellus stipticus
 
  • Studying luminescence mechanism of luminous fungi

 

      
 
  • Studying biosynthetic origin of marine luciferins: coelenterazine and Cypridina luciferin

 

           
 
Cypridina hilgendorfii
 
  • Developing fluorogenic sensors to important protein targets
 
 
FULFILLED
 
2009-2011
 
Biosynthetic mechanism of chemically unstable acylimine chromophore of red fluorescent proteins was investigated. This required development of new synthetic strategy to 2-acylaminoimidazolones - biosynthetic precursors of 2-acyliminoimidazolones. We have shown spontaneous oxidation of precursors with air oxygen by unusual mechanism.
             
Discosoma
 
2002-2009
 
Total synthesis of chromophores of GFP-like fluorescent proteins was used as a tool for independent structure determination of these chromophores. Also, this allowed to study structure-spectral properties relationship within this range of imidazole derivatives and to develop novel synthetic approaches to 2-functionalized arylideneimidazolones. Chromophores of AsFP595, Kaede and YFP538 were synthesized.
 
           
Zoanthus
 
           
Trachyphyllia
 
 
           
 
Anemonia
 
2002-2004
 
A blue proteinaceous pigment from Rhizostoma pulmo (jellyfish from the Black Sea) was isolated, sequenced and studied by biochemical methods. An attempt to determine the nature of the blue coloration (chromophore) was unsuccessful.
 
           
 
Black Sea jellyfish Rhizostoma pulmo possessing an unidentified blue pigment
 

Selected publications (show all)

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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
  • E-mail: ivyamp@ibch.ru

Scientists uncovered a mechanism of fungal luminescence and created luminescent yeasts (2018-11-30)

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.

Publications

  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

Mechanism of Fungal Bioluminescence study (2016-11-24)

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.

Publications

  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

Synthesis of the core structure of fungal terpenoid Panal - a component of bioluminescent fungus Panellus stipticus (2016-11-24)

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.

Publications

  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

The mechanism of bioluminescence of siberian worm Fridericia heliota was studied (2016-03-30)

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 (2016-03-30)

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.

Publications

  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