Group of fungal genetic engineering

 eldarov_1 Michael A. Eldarov
Head of the Group
INB, room 401
Телефон +7 (499) 135-62-19

Our group is interested in rather diverse aspects of regulation of primary and secondary metabolism in yeast and fungi. The main topic is the study of molecular control of  secondary metabolite production (cephalosporin C, lovastatin) in filamentous fungi Acremonium chrysogenum and Aspergills terreus with the focus of biogenic polyamines as inducer of antibiotic production, cell survival and stress resistance in these fungi. We have developed agrobacterim-mediated transformation system for industrial A.chrysogenum  and A.terreus strains,  determined  the dynamics of gene expression of key antibiotic biosynthesis and transport genes in these fungi, definied differences  in some biochemical, morphological, molecular genetic, physiological properties of industrial fungal trains, associated with their high producing phenotype.

We also collaborate with our partners in the field of enzymology of phosphorus metabolism in yeast and fungi (G.K.Skryabin Institute, Puschino), protein engineering of the enzymes of biotransformation of beta-lactam antibiotics and sperm-specific glyceraldehyde-phosphate dehydrogenase (Belozersky Institute, MSU).

Particularly, we have developed efficient expression systems for production of recombinant PPX1,PPN1, PPN2, DDP1 – yeast enzymes of polyphosphate metabolism, detailed their enzymatic properties.  Structural basis of substrate specificity of and quaternary structure formation were determined for Brevundimonas diminuta  glutaryl-acylase and novel more efficient analogs of this enzyme were prepared.

In collaboration with the group of genomics of microorganisms  we have deciphered mitochondrial genomes of several yeast and fungi, that helped to compared patterns of evolution of mitochondrial and nuclear genomes in several yeast species.

Molecular-genetic, physiological properties of  flor yeast strains, related to their ability to perform biological wine aging, have been identified using comparative genomics methods. Molecular markers of flor yeast strains have been identified (together with the department of genetics of microorganisms, NIIViV Magarach).



Selected publications:

  1. Zakirelev OI, Lomonoence on polype sequence and analysis of the mitochondrial genome of the methylotrophic yeast Hansenula polymorpha DL-1. FEMS Yeast Res. 2011 Sep;11(6):464-72.•Andreeva N, Ryazanova L, Zvonarev A, Trilisenko L, Kulakovskaya T, Eldarov M. Inorganic polyphosphate in methylotrophic yeasts. Appl Microbiol Biotechnol. 2018 Jun;102(12):5235-5244
  2. Andreeva N, Trilisenko L, Eldarov M, Kulakovskaya T. Polyphosphatase PPN1 of Saccharomyces cerevisiae: switching of exopolyphosphatase and endopolyphosphatase activities. PLoS One. 2015 Mar 5;10(3)
  3. Dumina MV, Zhgun AA, Kerpichnikov IV, Domracheva AG, Novak MI, Valiakhmetov AIa, Knorre DA, Severin FF, Él’darov MA, Bartoshevich IuÉ. [Functional characteristic of the CefT transporter of the MFS family involved in the transportation of beta-lactam antibiotics in Acremonium chrysogenum and Saccharomyces cerevisiae]. Prikl Biokhim Mikrobiol. 2013 Jul-Aug;49(4):372-81
  4. Dumina MV, Zhgun AA, Novak MI, Domratcheva AG, Petukhov DV, Dzhavakhiya VV, Eldarov MA, Bartoshevitch IE. 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 J.Microbiol Biotechnol. 2014 Nov;30(11):2933-41
  5. Eldarov MA, Beletsky AV, Tanashchuk TN, Kishkovskaya SA, Ravin NV, Mardanov AV. Whole-Genome Analysis of Three Yeast Strains Used for Production of Sherry-Like Wines Revealed Genetic Traits Specific to Flor Yeasts. Front Microbiol. 2018 May 15;9:965
  6. Eldarov MA, Kishkovskaia SA, Tanaschuk TN, Mardanov AV. Genomics and Biochemistry of Saccharomyces cerevisiae Wine Yeast Strains. Biochemistry (Mosc). 2016 Dec;81(13):1650-1668
  7. Kuravsky M, Barinova K, Marakhovskaya A, Eldarov M, Semenyuk P, Muronetz V, Schmalhausen E. Sperm-specific glyceraldehyde-3-phosphate dehydrogenase is stabilized by additional proline residues and an interdomain salt bridge. Biochim Biophys Acta. 2014 Aug 1;1844(10):1820-1826
  8. Meshcheriakova IuA, El’darov MA, Migunov AI, Stepanova LA, Repko IA, Kiselev OI, Lomonosov DP, Skriabin KG. [Cowpea mosaic virus chimeric particles bearing ectodomain of matrix protein 2 (M2E) of influenza A virus: production and  characteristics]. Mol Biol (Mosk). 2009 Jul-Aug;43(4):741-50
  9. Skryabin KG, El’darov MA, Kamardinov DK, Zinov’eva MV, Ivanov DS, Prasolov VS, Matskeplishvili ST, Busiashvili IuI, Petrov RV, Bokeriia LA, Kirpichnikov MP. Differential expression of the isoforms of human vascular endothelial growth factor and new approaches to therapeutic angiogenesis. Dokl Biol Sci. 2004 Jul-Aug;397:298-300
  10. Sokolov NN, Eldarov MA, Pokrovskaya MV, Aleksandrova SS, Abakumova OY, Podobed OV, Melik-Nubarov NS, Kudryashova EV, Grishin DV, Archakov AI. [Bacterial recombinant L-asparaginases: properties, structure and anti-proliferative activity]. Biomed Khim. 2015 May-Jun;61(3):312-24
  11. Zhdanov, D. D., Pokrovsky, V. S., Pokrovskaya, M. V, Alexandrova, S. S., Eldarov, M. A., Grishin, D. V, … Sokolov, N. N. (2017). Inhibition of telomerase activity and induction of apoptosis by Rhodospirillum rubrum L-asparaginase in cancer Jurkat cell line and normal human CD4+ T lymphocytes. Cancer medicine, 6(11), 2697–2712
  12. Zhgun AA, Ivanova MA, Domracheva AG, Novak MI, El’darov MA, Skriabin KG, Bartoshevich IuE. [Genetic transformation of the mycelium fungi Acremonium chrysogenum]. Prikl Biokhim Mikrobiol. 2008 Nov-Dec;44(6):663-70. Russian.