Group of fungal genetic engineering

  Alexander A. Zhgun
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. Eldarov M.A., Beletsky A.V., Tanashchuk T.N., Kishkovskaya S.V., Ravin N.V., Mardanov A.V. Whole-genome analysis of three yeast strains used for production of sherry-like wines revealed genetic traits specific to flor yeasts. Frontiers in Microbiology. 2018; Vol.9: e965. DOI: 10.3389/fmicb.2018.00965.
  2. Mardanov A.V, Beletsky A.V, Eldarov M.A, Tanashuk T.N., Kishkovskaya S.A., Ravin N.V. Draft genome sequence of the wine yeast strain Saccharomyces cerevisiae I-328. Microbiology Resource Announcements. 2018; 6(5): e01520-17. DOI: 10.1128/genomeA.01520-17.
  3. Andreeva N., Ryazanova L., Zvonarev A., Trilisenko L., Kulakovskaya T., Eldarov M. Inorganic polyphosphate in methylotrophic yeasts. Applied Microbiology and Biotechnology. 2018; 102(12): 5235-5244. DOI: 10.1007/s00253-018-9008-3.
  4. Turaev A.V., Tsvetkov V.B., Tankevich M.V., Smirnov I.P., Aralov A.V., Pozmogova G.E., Varishuk A.M.. Benzothiazole-based cyanines as fluorescent “light-up” probes for duplex and quadruplex DNA. Biochimie. 2019; Vol.162: 216-228. DOI: 10.1016/j.biochi.2019.04.018.
  5. Tsvetkov V.B., Zatsepin T.S.,. Turaev A.V., Farzan V.M., Pozmogova G.E., Aralov A.V., Varizhuk A. M.. DNA i-Motifs With Guanidino-i-Clamp Residues: The Counterplay Between Kinetics and Thermodynamics and Implications for the Design of pH Sensors. Computational and Structural Biotechnology Journal. 2019; Vol.17: 527-536. DOI: 10.1016/j.csbj.2019.04.006.
  6. Andreeva N., Ledova L., Ryasanova L., Kulakovskaya T., Eldarov M. The acid phosphatase Pho5 of Saccharomyces cerevisiae is not involved in polyphosphate breakdown. Folia Microbiologica. 2019; 64(6): 867-873. DOI: 10.1007/s12223-019-00702-6.
  7. Andreeva N., Ledova L., Ryazanova L., Tomashevsky A., Kulakovskaya T., Eldarov M. Ppn2 endopolyphosphatase overexpressed in Saccharomyces cerevisiae: Comparison with Ppn1, Ppx1, and Ddp1 polyphosphatases. Biochimie. 2019; Vol.163: 101-107. DOI: 10.1016/j.biochi.2019.06.001.
  8. Alexander Zhgun, Darya Avdanina, Kirill Shumikhin, Nikolay Simonenko, Elena Lyubavskaya, Ivan Volkov, Victor Ivanov. Detection of potential biodeterioration risks for tempera painting in 16th century exhibits from State Tretyakov Gallery. PLoS ONE. 2020; 15(4): e0230591. DOI: 10.1371/journal.pone.0230591.
  9. Mardanov A.V., Eldarov M.A., Beletsky A.V, Tanashchuk T.N., Kishkovskaya S.A., Ravin N.V. Transcriptome Profile of Yeast Strain Used for Biological Wine Aging Revealed Dynamic Changes of Gene Expression in Course of Flor Development. Frontiers in Microbiology. 2020; Vol.11: 538. DOI: 10.3389/fmicb.2020.00538.
  10. Dumina M. V., Eldarov M.A., Zdanov D.D., Sokolov N.N. L-аспарагиназы экстремофильных микроорганизмов в биомедицине. Биомедицинская химия. 2020; 66(2): 105-123. DOI: 10.18097/PBMC20206602105.
  11. Zhgun A.A., Avdanina D.A., Shagdarova B.Ts., Troyan E.V., Nuraeva G.K., Potapov M.P., Il’Ina A.V., Shitov M.V., Varlamov V.P. Search for Efficient Chitosan-Based Fungicides to Protect the 15th‒16th Centuries Tempera Painting in Exhibits from the State Tretyakov Gallery. Microbiology (Mikrobiologiya). 2020; 89(6): 750-755. DOI: 10.1134/S0026261720060193.
  12. Barinova K.V, Serebryakova M.V, Eldarov M.A. Kulikova A.A., Mitkevich V.A., Muronetz V.I., Schmalhausen E.V. S-glutathionylation of human glyceraldehyde-3-phosphate dehydrogenase and possible role of Cys152-Cys156 disulfide bridge in the active site of the protein. Biochimica et Biophysica Acta: Gene Regulatory Mechanisms. 2020; 1864(6): 129560. DOI: 10.1016/j.bbagen.2020.129560.
  13. Alexander Zhgun, Mariya Dumina, Ayrat Valiakhmetov, Mikhail Eldarov. The critical role of plasma membrane H+-ATPase activity in cephalosporin C biosynthesis of Acremonium chrysogenum. PLoS ONE. 2020; 15(8): e0238452. DOI: 10.1371/journal.pone.0238452.
  14. Mervi T. Hyvönen, Tuomo A. Keinänen, Gulgina K. Nuraeva, Dmitry V. Yanvarev, Maxim Khomutov, Elena N. Khurs, Sergey N. Kochetkov, Jouko Vepsäläinen, Alexander A. Zhgun, Alex R. Khomutov. Hydroxylamine Analogue of Agmatine: Magic Bullet for Arginine Decarboxylase. Biomolecules. 2020; 10(3): 406. DOI: 10.3390/biom10030406.
  15. Eldarov M.A., Mardanov A.V. Metabolic engineering of wine strains of Saccharomyces cerevisiae. Genes. 2020; 11(9): 964. DOI: 10.3390/genes11090964.
  16. Alexander A. Zhgun, Gulgina K. Nuraeva, Ivan A. Volkov. High-Yielding Lovastatin Producer Aspergillus terreus Shows Increased Resistance to Inhibitors of Polyamine Biosynthesis. Applied Sciences (Switzerland). 2020; 10(22): 8290. DOI: 10.3390/app10228290.