Group of Biotechnology of Physiologically Active Compounds

 

Vakhtang V. Dzhavakhiya
Ph.D.
Head of Group
INB, room 100/1

 

Телефон +7 (499) 135-90-01
E-Mail  dzhavakhiya@biengi.ac.ru

Main research activities

  1. Strain selection to obtain superproducers of physiologically active compounds
  2. Development and optimization of fermentation processes for industrial strains
  3. Development of new methods of separation and purification of biosynthetic products
  4. Development of industrial regulations for the production of pharmaceutical substances
  5. Development of methods for a rational selection of strains with changed metabolism and/or development cycle
  6. Development of new approaches to control the industrial biosynthesis of physiologically active compounds
  7. Development of biotechnological methods for the synthesis of steroid preparations from plant sterols
  8. Study of the processes of microbiological transformation of steroids and development of original steroid-transforming strains
  9. Synthesis and study of the biological activity of new modified steroids
  10. Study of the regulation of secondary metabolite biosynthesis in mycelial fungi.


Main achievements

Laboratory of Biotechnology of Physiologically Active Compounds

Since 2012 the lab successfully completed nine projects on the development of methods for the biosynthesis, separation, and purification of various pharmaceutical substances (the total cost of the projects exceeded 30 mln. RUR) including:

  • Development of optimal schemes of the multi-stage induced mutagenesis to obtain highly-productive strains of fungi, actinomycetes, and bacteria;
  • Obtaining of highly productive mutant strains from wild strains for the industrial production of such substances as compactin and polymyxin B, and the development of corresponding technologies for the separation and purification of these compounds;
  • Development of a strain able to produce rifamycin B using a new substrate, diethylmalonic acid monoureide;
  • Development of laboratory and industrial regulations for the biosynthesis of tobramycin and josamycin pharmaceutical substances and the quality control methods for their production;
  • Development of a new technology of the 6a-methylprednisolone synthesis from 6a-methylhydrocortisone.

Group of Fungal Bioengineering (joint studies with the Group of genetic engineering of fungi)

  • Development of a new method of cephalosporin C biosynthesis using a new Acremonium chrysogenum strain VKM F-4081D;
  • Optimization of the general protocol of agrobacterial transformation of A. chrysogenum strains;
  • Characterization of CefT protein functions in the regulation of cephalosporin C production in A. chrysogenum;
  • Determination of the effect of exogenous polyamines on the level of cephalosporin C production and expression of the corresponding biosynthetic and regulation genes in A. chrysogenum.

Group of biotechnology of Steroids

  • Development of new methods of the directed hydroxylation of steroids;
  • Development of original biotechnological methods of the 9a-hydroxylation and 1,2-dehydration of pharmaceutical steroids using biocatalysts based on actinomycetes Rhodococcus erythropolis and Pimelobacter simplex;
  • Optimization of microbiological synthesis of 17-ketoandrostans for the steroid production under industrial scale;
  • Development of the technologies for the biosynthesis of hydrocortisone, spironolacton, metandrostenolone, prednisolone, and methylprednisolone;
  • Development of the industrial regulations for the biosynthesis of medroxyprogesteron;
  • Synthesis and study of mepregenol esters, unique gestagens used in the treatment of hormone-dependent tumors, and revealing of new analogues with high contraceptive and gestagenic activity, including one substance – mepregenol capronate – having a high antitumor activity.

Number of patents: 19.


Selected publications (since 2010)

  1. Dzhavakhiya V., Savushkin V., Ovchinnikov A., Glagolev V., Savelyeva V., Popova E., Novak N., Glagoleva E. (2016) Scaling up a virginiamycin production by a high-yield Streptomyces virginiae VKM AC-2738D strain using adsorbing resin addition and fed-batch fermentation iunder controlled conditions. 3 Biotech, 6(2): Article ID 240.
  2. Savushkin V.A., Dzhavakhiya V.V., Glagoleva E.V., Savel’eva V.V., Popova E.D., Ovchinnikov A.I., Glagolev V.I., Novak N.V., Durnikin D.A. (2016) Development of highly active virginiamycin-producing strain and improvement of its productivity using synthetic adsorbing resins. Biological Bulletin of Bogdan Chmelnitskiy Melitopol State Pedagogical University, 6(3): 195-208.
  3. Karpova N.V., Andryushina V.A., Stytsenko T.S., Druzhinina A.V., Feofanova T.D., Kurakov A.V. (2016) A search for microscopic fungi with directed hydroxylase activity for the synthesis of steroid drugs. Applied Biochemistry and Microbiology, 52(3): 316-323.
  4. Dzhavakhiya V.V., Voinova T.M., Glagoleva E.V., Petukhov D.V., Ovchinnikov A.I., Kartashov M.I., Kuznetsov B.B., Skryabin K.G. (2015) Strain improvement of Streptomyces хanthochromogenes RIA 1098 for enhanced pravastatin production at high compactin concentrations. Indian Journal of Microbiology, 55(4): 440-446.
  5. Andryushina V.A., Karpova N.V., Druzhinina A.V., Stytsenko T.S., Podorozhko E.A., Ryabev A.N., Lozinsky V.I. (2015) Novel immobilized biocatalyst formicrobiological synthesis of pharmaceutical steroids. Applied Biochemistry and Microbiology, 51(5): 530-538.
  6. Dzhavakhiya V.V., Glagoleva E.V., Petukhov D.V., Ovchinnikov A.I., Skryabin K.G. (2014) Improved method for the isolation and purification of polymyxin B. Russian Biopharmaceutical Journal, 6(3): 9-12.
  7. Dumina M.V., Zhgun A.A., Novak M.I., Domratcheva A.G., Petukhov D.V., Dzhavakhiya V.V., Eldarov M.A., Bartoshevitch Iu.E. (2014) Comparative gene expression profiling reveals key changes in expression levels of cephalosporin C biosynthesis and transport genes between low and high-producing strains of Acremonium chrysogenum. World Journal of Microbiology and Biotechnology, 30(11): 2933-2941.
  8. Zhgun A.A., Kalinin S.G., Dumina M.V., Novak M.I., Domracheva A.G., Dzhavakhiya V.V., Petuhov D.V., El’darov M.A., Bartoshevitch Y.E. (2013) Exogenous polyamines as inducers of beta-lactam biosynthesis in A. chrysogenum. FEBS Journal, 280(S1): 579.
  9. Andryushina V.A., Voishvillo N.E., Druzhinina A.V., Stytsenko T.S., Yaderets V.V., Petrosyan M.A., Zeinalov O.A. (2013) 14α-Hydroxylation of steroids by mycelium of the mold fungus Curvularia lunata (VKPM F-981) to produce precursors for synthesizing new steroidal drugs. Pharmaceutical Chemistry Journal, 47(2): 103-108.
  10. Dumina M.V., Zhgun A.A., Kerpichnikov I.V., Domracheva A.G., Novak M.I., Valiachmetov A.Ya., Knorre D.A., Severin F.F., Eldarov M.A., Bartoshevich Yu.E. (2013) Functional analysis of MFS protein CefT involved in the transport of beta-lactam antibiotics in Acremonium chrysogenum and Saccharomyces cerevisiae. Applied Biochemistry and Microbiology, 49(4): 368-377.
  11. Andryushina V.A., Yaderets V.V., Stytsenko T.S., Druzhinina A.V., Voishvillo N.E. (2013) Effect of the steroid molecule structure on the direction of its hydroxylation by the fungus Curvularia lunata. Applied Biochemistry and Microbiology, 49(4): 386-394.
  12. Eldarov M.A., Mardanov A.V., Beletsky A.V., Dzhavakhiya V.V., Ravin N.V., Skryabin K.G. (2012) Complete mitochondrial genome of compactin-producing fungus Penicillium solitum and comparative analysis of Trichocomaceae mitochondrial genomes. FEMS Microbiology Letters. 329(1): 9-17.
  13. Dumina M.V., Zhgun A.A., Domracheva A.G., Novak M.I., El’darov M.A. (2012) Chromosomal polymorphism of Acremonium chrysogenum strains producing cephalosporin C. Russian Journal of Genetics, 48(8): 778-784.
  14. Zeinalov O.A., Yaderets V.V., Stytsenko T.S., Petrosyan M.A., Andryushina V.A. (2012) Synthesis and biological activity of synthetic 17α-hydroxyprogesterone derivatives. Pharmaceutical Chemistry Journal, 46(4): 203-206.
  15. Savinova T.S., Nguyen T. Diep, Voishvillo N.E., Andryushina V.A., Karpova N.V., Beletskaya I.P., Luu D. Huy (2012) Extraction of a mixture of phytosterols from soybean processing by-product and its use in the manufacture of 9α-hydroxyandrost-4-en-3,17-dione. Pharmaceutical Chemistry Journal, 46(3): 183-186.
  16. Carpova-Rodina N.V., Andryushina V.A., Yaderets V.V., Druzhinina A.V., Stytsenko T.S., Shaskol’skiy B.L., Lozinsky V.I., Luu D. Huy, Voishvillo N.E. (2011) Transformation of Δ4-3-ketosteroids by free and immobilized cells of Rhodococcus erythropolis actinobacterium. Applied Biochemistry and Microbiology, 47(4): 386-392.
  17. Andryushina V.A., Druzhinina A.V., Yaderets V.V., Stytsenko T.S., Voishvillo N.E. (2011) Hydroxylation of steroids by Curvularia lunata mycelium in the presence of methyl-β-cyclodextrine. Applied Biochemistry and Microbiology, 47(1): 42-48.
  18. Kalebina T.S., Selyakh I.O., Gorkovskii A.A., Bezsonov E.E., El’darov M.A., Novak M.I., Domracheva A.G., Bartoshevich Yu.E (2010) Structure peculiarities of cell walls of Acremonium chrysogenum — an autotroph of cephalosporin C. Applied Biochemistry and Microbiology, 46(6): 614-619.
  19. Valiakhmetov A.Ya., Trilisenko L.V., Vagabov V.M., Bartoshevich Yu.E., Kulaev I.S., Novak M.I., Domracheva A.G., El’darov M.A., Skryabin K.G. (2010) The concentration dynamics of inorganic polyphosphates during the cephalosporin C synthesis by Acremonium chrysogenum. Applied Biochemistry and Microbiology, 46(2): 184-190.
  20. Andryushina V.A., Druzhinina A.V., Yaderets V.V., Stytsenko T.S., Voishvillo N.E. (2010) 7α-Hydroxylation of steroid 5-olefins by mold fungi. Applied Biochemistry and Microbiology, 46(1): 69-74.