Actinobacteria Metabolic Engineering

This group is located at the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS)

The growing resistance towards established antibiotics presents a serious problem especially with infectious diseases. The development of new drugs is mainly based on known molecules and mechanisms, which allows bacteria to assimilate rapidly. Hence, scientists are looking for novel drugs. At the Helmholtz Institute for Pharmaceutical Research Saarland (HIPS), a branch of the Helmholtz Centre for Infection Research (HZI) at Braunschweig, the researchers develop new pathways, by which they force actinomycetes to produce hitherto unknown compounds.

Leader

Selected Publications

Rebets Y, Nadmid S, Paulus C, Dahlem C, Herrmann J, Hübner H, Rückert C, Kiemer AK, Gmeiner P, Kalinowski J, Müller R, Luzhetskyy A. Perquinolines A-C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis. Angew Chem Int Ed Engl. 2019 Sep 9;58(37):12930-12934. doi:10.1002/anie.201905538.

Horbal L, Marques F, Nadmid S, Mendes MV, Luzhetskyy A. Secondary metabolites overproduction through transcriptional gene cluster refactoring. Metab Eng. 2018 Sep;49:299-315. doi: 10.1016/j.ymben.2018.09.010.

Myronovskyi M, Rosenkränzer B, Nadmid S, Pujic P, Normand P, Luzhetskyy A.Generation of a cluster-free Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters. Metab Eng. 2018 Sep;49:316-324. doi: 10.1016/j.ymben.2018.09.004.

Lopatniuk M, Myronovskyi M, Luzhetskyy A. Streptomyces albus: A New Cell Factory for Non-Canonical Amino Acids Incorporation into Ribosomally Synthesized  Natural Products. ACS Chem Biol. 2017 Sep 15;12(9):2362-2370. doi:10.1021/acschembio.7b00359.

Rebets Y, Brötz E, Manderscheid N, Tokovenko B, Myronovskyi M, Metz P, Petzke L, Luzhetskyy A. Insights into the pamamycin biosynthesis. Angew Chem Int Ed Engl. 2015 Feb 9;54(7):2280-4. doi: 10.1002/anie.201408901.

Publications

  • Rebets Y., Nadmid S., Paulus C., Dahlem C., Herrmann J., Hübner H., Rückert C., Kiemer A.K., Gmeiner P., Kalinowski J., Müller R., Luzhetskyy A. (2019) Perquinolines A-C: Unprecedented Bacterial Tetrahydroisoquinolines Involving an Intriguing Biosynthesis. Angew Chem Int Ed Engl. [Epub ahead of print].
  • Myronovskyi M., Luzhetskyy A. (2019) Heterologous production of small molecules in the optimized Streptomyces hosts. Nat Prod Rep. [Epub ahead of print].
  • Lopatniuk M., Myronovskyi M., Nottebrock A., Busche T., Kalinowski J., Ostash B., Fedorenko V., Luzhetskyy A. (2019) Effect of "ribosome engineering" on the transcription level and production of S. albus indigenous secondary metabolites. Appl Microbiol Biotechnol. 103(17):7097-7110.
  • Rebets Y., Tsolis K. C., Guðmundsdóttir E. E., Koepff J., Wawiernia B., Busche T., Bleidt A., Horbal L., Myronovskyi M., Ahmed Y., Wiechert W., Rückert C., Hamed M. B., Bilyk B., Anné J., Friðjónsson Ó., Kalinowski J., Oldiges M., Economou A., Luzhetskyy A. (2018) Characterization of Sigma Factor Genes in Streptomyces lividans TK24 Using a Genomic Library-Based Approach for Multiple Gene Deletions. Front Microbiol. 9(3033).
  • Rodríguez Estévez M., Myronovskyi M., Gummerlich N., Nadmid S., Luzhetskyy A. (2018) Heterologous Expression of the Nybomycin Gene Cluster from the Marine Strain Streptomyces albus subsp. chlorinus NRRL B-24108. Mar Drugs. 16(11): E435.
  • Horbal L., Marques F., Nadmid S., Mendes M. V., Luzhetskyy A. (2018) Secondary metabolites overproduction through transcriptional gene cluster refactoring. Metab Eng. 49: 299-315.
  • Myronovskyi M., Rosenkränzer B., Nadmid S., Pujic P., Normand P., Luzhetskyy A. (2018) Generation of a cluster-free Streptomyces albus chassis strains for improved heterologous expression of secondary metabolite clusters. Metab Eng. 49: 316-324.
  • Paulus C., Rebets Y., Zapp J., Rückert C., Kalinowski J., Luzhetskyy A. (2018) New Alpiniamides From Streptomyces sp. IB2014/011-12 Assembled by an Unusual Hybrid Non-ribosomal Peptide Synthetase Trans-AT Polyketide Synthase Enzyme. Front Microbiol. 9: 1959.
  • Busche T., Tsolis K. C., Koepff J., Rebets Y., Rückert C., Hamed M. B., Bleidt A., Wiechert W., Lopatniuk M., Yousra A., Anné J., Karamanou S., Oldiges M., Kalinowski J., Luzhetskyy A. (2018) Economou A. Multi-Omics and Targeted Approaches to Determine the Role of Cellular Proteases in Streptomyces Protein Secretion. Front Microbiol. 9: 1174.
  • Rebets Y., Schmelz S., Gromyko O., Tistechok S., Petzke L., Scrima A., Luzhetskyy A. (2018) Design, development and application of whole-cell based antibiotic-specific biosensor. Metab Eng. 47: 263-270.
  • Horbal L., Siegl T., Luzhetskyy A. (2018) A set of synthetic versatile genetic control elements for the efficient expression of genes in Actinobacteria. Sci Rep.8(1): 491.
  • Ahmed Y., Rebets Y., Tokovenko B., Brötz E., Luzhetskyy A. (2017) Identification of butenolide regulatory system controlling secondary metabolism in Streptomyces albus J1074. Sci Rep. 7 (1): 9784.
  • Lopatniuk, M., Myronovskyi, M., Luzhetskyy, A. (2017) Streptomyces albus: A New Cell Factory for Non-Canonical Amino Acids Incorporation into Ribosomally Synthesized Natural Products, ACS Chem Biol. 12 (9): 2362-2370.
  • Ahmed, Y., Rebets, Y., Tokovenko, B., Brötz, E., Luzhetskyy, A. (2017) Identification of butenolide regulatory system controlling secondary metabolism in Streptomyces albus J1074, Sci Rep. 7 (1): 9784.
  • Tokovenko, B., Rückert, C., Kalinowski, J., Mohammadipanah, F., Wink, J., Rosenkränzer, B., Myronovskyi, M., Luzhetskyy,A. (2017) Complete Draft Genome Sequence of the Actinobacterium Nocardiopsis sinuspersici UTMC102 (DSM 45277T), Which Produces Serine Protease, Genome Announc., 5 (20)
  • Paulus, C., Rebets, Y., Tokovenko, B., Nadmid, S., Terekhova, L.P., Myronovskyi, M., Zotchev, S.B., Ruckert, C., Braig, S., Zahler, S., Kalinowski, J. and Luzhetskyy, A. (2017) New natural products identified by combined genomics-metabolomics profiling of marine Streptomyces sp. MP131-18, Scientific reports, 7: 42382.
  • Bilyk, B., Horbal, L., Luzhetskyy, A. (2017) Chromosomal position effect influences the heterologous expression of genes and biosynthetic gene clusters in Streptomyces albus J1074, Microbial cell factories, 16 (1): 5.
  • Myronovskyi M., Luzhetskyy A. (2016) Native and engineered promoters in natural product discovery. Nat Prod Rep. 33 (8): 1006-19.
  • Myronovskyi, M., Brötz, E., Rosenkränzer, B., Manderscheid, N., Tokovenko, B., Rebets, Y., Luzhetskyy, A. (2016) Generation of new compounds through unbalanced transcription of landomycin A cluster. Appl Microbiol Biotechnol. [Epub ahead of print]
  • Bilyk, O., Sekurova, O.N., Zotchev, S.B., Luzhetskyy, A. (2016) Cloning and Heterologous Expression of the Grecocycline Biosynthetic Gene Cluster. PLoS One. 13; 11(7): e0158682.
  • Manderscheid, N., Bilyk, B., Busche, T., Kalinowski, J., Paululat, T., Bechthold, A., Petzke, L., Luzhetskyy, A. (2016) An influence of the copy number of biosynthetic gene clusters on the production level of antibiotics in a heterologous host. J Biotechnol. 232: 110-7.
  • Bilyk, O., Luzhetskyy, A. (2016) Metabolic engineering of natural product biosynthesis in actinobacteria. Curr Opin Biotechnol. 42: 98-107.
  • Horbal, L., Luzhetskyy, A. (2016) Dual control system - A novel scaffolding architecture of an inducible regulatory device for the precise regulation of gene expression. Metab Eng. 37: 11-23.
  • Bilyk, O., Brötz, E., Tokovenko, B., Bechthold, A., Paululat, T., Luzhetskyy, A. (2015) New Simocyclinones: Surprising Evolutionary and Biosynthetic Insights. ACS Chem Biol. 11 (1): 241-50.
  • Axenov-Gribanov, D., Rebets, Y., Tokovenko, B., Voytsekhovskaya, I., Timofeyev, M., Luzhetskyy, A. (2015) The isolation and characterization of actinobacteria from dominant benthic macroinvertebrates endemic to Lake Baikal. Folia Microbiol (Praha). 61 (2): 159-168.
  • Brötz, E., Bilyk, O., Kröger, S., Paululat, T., Bechthold, A., Luzhetskyy, A. (2014)Amycomycins C and D, new angucyclines from Kitasatospora sp. Tetrahedron Letters. 55(42): 5771–5773.
  • Rebets, Y., Brötz, E., Manderscheid, N., Tokovenko, B., Myronovskyi, M., Metz, P., Petzke, L., Luzhetskyy, A. (2014) Insights into the Pamamycin Biosynthesis. Angew Chem Int Ed Engl. 54 (7): 2280‐4.
  • Rebets, Y., Tokovenko, B., Lushchyk, I., Rückert, C., Zaburannyi, N., Bechthold, A., Kalinowski, J., Luzhetskyy, A. (2014) Complete genome sequence of producer of the glycopeptide antibiotic Aculeximycin Kutzneria albida DSM 43870T, a representative of minor genus of Pseudonocardiaceae. BMC Genomics. 15: 885.
  • Myronovskyi, M., Rosenkränzer, B., Luzhetskyy, A. (2014) Iterative marker excision system. Appl Microbiol Biotechnol. 98 (10): 4557‐70.
  • Horbal, L., Fedorenko, V., Luzhetskyy, A. (2014) Novel and tightly regulated resorcinol and cumate‐inducible expression systems for Streptomyces and other actinobacteria. Appl Microbiol Biotechnol. 98 (20): 8641‐55.
  • Bilyk, B. and Luzhetskyy A. (2014) Unusual site‐specific DNA integration into the highly active pseudo‐attB of the Streptomyces albus J1074 genome Appl Microbiol Biotechnol. 98(11): 5095‐104.Zaburannyi, N., Rabyk, M., Ostash, B., Fedorenko, V. and Luzhetskyy, A. (2014) Insights into naturally minimised Streptomyces albus J1074 genome BMC Genomics, 15 (1): 97.
  • Myronovskyi, M., Tokovenko, B., Brötz, E., Rückert, C., Kalinowski, J. and Luzhetskyy, A. (2014) Genome rearrangements of Streptomyces albus J1074 lead to the carotenoid gene cluster activation Appl. Microbiol. Biotechnol., 98 (2): 795‐806.Rebets, Y., Brötz, E., Tokovenko, B. and Luzhetskyy, A. (2014) Actinomycetes biosynthetic potential: how to bridge in silico and in vivoJournal of Industrial Microbiology & Biotechnology, 41 (2): 387‐402.
  • Siegl, T., Tokovenko, B., Myronovskyi, M., and Luzhetskyy, A. (2013) Design, constructionand characterisation of a synthetic promoter library for fine‐tuned gene expression inactinomycetes. Metabolic Engineering, 19: 98‐106.Myronovskyi, M., Tokovenko, B., Manderscheid, N., Petzke, L., and Luzhetskyy, A. (2013)Complete genome sequence of Streptomyces fulvissimus. Journal of Biotechnology,168(1):117‐118.
  • Myronovskyi, M and Luzhetskyy, A. (2013) Genome engineering in actinomycetes using site‐specific recombinases. Applied Microbiology and Biotechnology, 97 (11): 4701‐4712.
  • Bilyk, B., Weber, S., Myronovskyi, M., Bilyk, O., Petzke, L. and Luzhetskyy, A. (2013) In vivo random mutagenesis of streptomycetes using mariner‐based transposon Himar1. Applied Microbiology and Biotechnology, 97 (1): 351‐359.
  • Horbal, L., Fedorenko, V., Bechthold, A. and Luzhetskyy, A. (2013) A transposon‐based strategy to identify the regulatory gene network responsible for landomycin E biosynthesis. FEMS Microbiology Letters, 342 (2): 138‐146.
  • Siegl, T. and Luzhetskyy, A. (2012) Actinomycetes genome engineering approaches. Antonie Van Leeuwenhoek, 102 (3): 503‐516.
  • Herrmann, S., Siegl, T., Luzhetska, M., Petzke, L., Jilg, C., Welle, E., Erb, A., Leadlay, P.F., Bechthold, A. and Luzhetskyy, A. (2012) Site‐specific recombination strategies for engineering actinomycete genomes. Applied and Environmental Microbiology, 78 (6): 1804‐1812.
  • Myronovskyi, M., Welle, E., Fedorenko, V. and Luzhetskyy, A. (2011) Beta‐glucuronidase as a sensitive and versatile reporter in actinomycetes. Applied and Environmental Microbiology, 77 (15): 5370‐5383.
  • Siegl, T., Petzke, L., Welle, E., and Luzhetskyy, A. (2010) I‐SceI endonuclease: a new tool for DNA repair studies and genetic manipulations in streptomycetes. Applied Microbiology and Biotechnology, 87 (4): 1525‐1532.
  • Petzke, L. and Luzhetskyy, A. (2009) In vivo Tn5‐based transposon mutagenesis of Streptomycetes. Applied Microbiology and Biotechnology, 83 (5): 979‐986.
  • Fedoryshyn, M., Petzke, L., Welle, E., Bechthold, A. and Luzhetskyy, A. (2008) Marker removal from actinomycetes genome using Flp recombinase. Gene, 419 (1‐2): 43‐47.
  • Fedoryshyn, M., Welle, E., Bechthold, A. and Luzhetskyy, A. (2008) Functional expression of the cre recombinase in actinomycetes. Applied Microbiology and Biotechnology, 78 (6): 1065‐1070.
  • Luzhetskyy, A., Hoffman, J., Pelzer, S., Wohlert, S., Vente, A. and Bechthold, A. (2008) Aranciamycin analogues generated by combinatorial biosynthesis show improved antitumor activity. Applied Microbiology and Biotechnology, 80(1): 15‐19.
  • Luzhetskyy, A., Weiss, H., Charge, A., Welle, E., Linennbrink, A. and Bechthold, A. (2007) A strategy for cloning glycosyltransferase genes involved in natural product biosynthesis. Applied Microbiology and Biotechnology, 75 (6): 1367‐1375.
  • Luzhetskyy, A., Mayer, A., Hoffmann, J., Pelzer, S., Wohlert, S., Vente, A. and Bechthold, A. (2007) Cloning and heterologous expression of the aranciamycin biosynthetic gene cluster revealed a new flexible glycosyltransferase. ChemBioChem, 8 (6): 599‐602.
  • Luzhetskyy, A., Fedoryshyn M., Gromyko O., Ostash B., Rebets Y., Bechthold A. and Fedorenko V. (2006) IncP plasmids are most effective in mediating conjugation between Escherichia coli and Streptomycetes. Russian Journal of Genetics, 42 (5): 476‐481.
  • Luzhetskyy, A. and Bechthold, A. (2005) It works: combinatorial biosynthesis for generatingnovel glycosylated compounds. Molecular Microbiology, 58 (1): 3‐5.
  • Luzhetskyy, A., Taguchi, T., Fedoryshyn, M., Dürr, C., Wohlert, S.E., Novikov, V. and Bechthold, A. (2005) LanGT2 catalyzes the first glycosylation step during Landomycin A biosynthesis. ChemBioChem, 6 (8): 1406‐1410.
  • Luzhetskyy, A., Fedoryshyn, M., Dürr, C., Taguchi, T., Novikov, V. and Bechthold, A. (2005) Iteratively acting glycosyltransferases involved in the hexasaccharide biosynthesis of Landomycin A. Chemistry & Biology, 12 (7): 725‐729.
  • Luzhetskyy, A., Zhu, L., Gibson, M., Fedoryshyn, M., Dürr, C., Hofmann, C., Hoffmeister, D.,Ostash, B., Mattingly, C., Adams, V., Fedorenko, V., Rohr, J. and Bechthold, A. (2005) Generation of novel Landomycins M and O through targeted gene disruption. ChemBioChem, 6 (4): 675‐678.
  • Luzhetskyy, A., Liu, T., Fedoryshyn, M., Ostash, B., Fedorenko, V., Rohr, J. and Bechthold, A. (2004) Function of lanGT3, a glycosyltransferase gene involved in Landomycin A biosynthesis. ChemBioChem, 5 (11): 1567‐1570.
  • Luzhetskyy, A., Fedoryshyn, M., Hoffmeister, D., Bechthold, A. and Fedorenko, V. (2002) Gene cloning system for Streptomyces cyanogenus S136. Visn.Lviv.Univ., 29, 62‐68.
  • Luzhetskyy, A., Ostash B.E. and Fedorenko V.A. (2001) Intergeneric Conjugation Escherichia coli–Streptomyces globisporus 1912 using integrative plasmid pSET152 and its derivatives / Interspecies conjugation of Escherichia coli‐Streptomyces globisporus 1912 using integrative plasmid pSET152 and its derivatives. Russian Journal of Genetics / Genetika, 37 (10): 1123‐1129 / 1340‐1347.

 Reviews and Book Chapters

  • Rebets, Y., Kormanec, J., Luzhetskyy, A., Bernaerts, K. and Anné, J. (2017) Cloning and Expression of Metagenomic DNA in Streptomyces lividans and Subsequent Fermentation for Optimized Production, Methods in molecular biology (Clifton, N.J.), 99-144.
  • Luzhetskyy, A., Bilyk, O. (2017) Host Organism: Streptomyces. In: Christoph Wittmann (Editor) Industrial Biotechnology: Microorganisms, Volume 2, Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim, Germany, Part IV, chapter 13: 487-504.
  • Luzhetskyy, A., Weitnauer, G., Bechthold, A. (2012) Prokaryotic Cells in Biotech Production. In: Kayer, O. and Warzecha, H. (Eds) Pharmaceutical Biotechnology: Pharmaceutical Biotechnology: Drug Discovery and Clinical Applications, Second Edition, Wiley-VCH Verlag GmbH & Co. KGaA Weinheim, Germany, chapter 2: 15-41.
  • Luzhetskyy, A., Pelzer, S., Bechthold, A. (2007) The future of natural products as a source of new antibiotics. Curr Opin Investig Drugs. 8 (8): 608‐613.
  • Luzhetskyy, A., Vente, A, Bechthold, A. (2005) Glycosyltransferases involved in the biosynthesis of biologically active natural products that contain oligosaccharides. Mol.Biosyst. 1 (2): 117‐126.
  • Luzhetskyy, A., Mendez, C., Salas, J.A., Bechthold, (2008) A. Glycosyltransferases, important tools for drug design. Curr Topics Med Chem. 8 (8): 680‐709.
  • Luzhetskyy, A. and Bechthold, A. (2008) Features and applications of bacterial glycosyltransferases: current state and prospects. Appl Microbiol Biotechnol. 80 (6): 945‐952.
  • Hertweck, C., Luzhetskyy, A., Rebets, Y., Bechthold, A. (2007) Type II polyketide synthases: gaining a deeper insight into enzymatic teamwork. Nap Prod Rep. 24 (1): 162‐190.
  • Mendez, C., Luzhetskyy, A., Bechthold, A., Salas, J.A. (2008) Deoxysugars in bioactivenatural products: development of novel derivatives by altering the sugar pattern. Curr Topics Med Chem. 8 (8): 710‐724.
  • Bechthold, A., Weitnauer, G., Luzhetskyy, A., Berner, M., Bihlmeier, C., Boll, R., Durr, C., Frerich, A., Hofmann, C., Mayer, A., Treede, I., Vente, A., Luzhetska, M. (2005) Glycosyltransferases and other tailoring enzymes as tools for the generation of novel compounds. Ernst Schering Research Foundation Workshop. 51: 147‐163.

 Selected publications as a co‐author

  • Kuzhyk Y., Lopatniuk M., Luzhetskyy A., Fedorenko V., Ostash B. (2019) Genome Engineering Approaches to Improve Nosokomycin A Production by Streptomyces ghanaensis B38.3. Indian J Microbiol. 59(1):109-111.
  • Koshla O., Yushchuk O., Ostash I., Dacyuk Y., Myronovskyi M., Jäger G., Süssmuth R.D., Luzhetskyy A., Byström A., Kirsebom L.A., Ostash B. (2019) Gene miaA for post-transcriptional modification of tRNA(XXA) is important for morphological and metabolic differentiation in Streptomyces. Mol Microbiol. 112(1):249-265.
  • Kuzhyk Y., Lopatniuk M., Luzhetskyy A., Fedorenko V., Ostash B.(2019) Genome Engineering Approaches to Improve Nosokomycin A Production by Streptomyces ghanaensis B38.3. Indian J Microbiol. 59 (1): 109-111.
  • Hamed M. B., Vrancken K., Bilyk B., Koepff J., Novakova R., van Mellaert L., Oldiges M., Luzhetskyy A., Kormanec J., Anné J., Karamanou S., Economou A. (2018) Monitoring Protein Secretion in Streptomyces Using Fluorescent Proteins. Front Microbiol. 9: 3019
  • Sehin Y., Koshla O., Dacyuk Y., Zhao R., Ross R., Myronovskyi M., Limbach P. A., Luzhetskyy A., Walker S., Fedorenko V., Ostash B. (2019) Gene ssfg_01967 (miaB) for tRNA modification influences morphogenesis and moenomycin biosynthesis in Streptomyces ghanaensis ATCC14672. Microbiology. 165 (2): 233-245.
  • Yushchuk O., Ostash I., Vlasiuk I., Gren T., Luzhetskyy A., Kalinowski J., Fedorenko V., Ostash B. (2018) Heterologous AdpA transcription factors enhance landomycin production in Streptomyces cyanogenus S136 under a broad range of growth conditions. Appl Microbiol Biotechnol. 102 (19): 8419-8428.
  • Barton N., Horbal L., Starck S., Kohlstedt M., Luzhetskyy A., Wittmann C. (2018) Enabling the valorization of guaiacol-based lignin: Integrated chemical and biochemical production of cis,cis-muconic acid using metabolically engineered Amycolatopsis sp ATCC 39116. Metab Eng. 45: 200-210.
  • Koshla O., Yushchuk O., Ostash I., Dacyuk Y., Myronovskyi M., Jäger G., Süssmuth R.D., Luzhetskyy A., Byström A., Kirsebom L.A., Ostash B. (2019) Gene miaA for post-transcriptional modification of tRNA(XXA) is important for morphological and metabolic differentiation in Streptomyces. Mol Microbiol. 112(1):249-265.
  • Protasov, E., Axenov-Gribanov, D., Rebets, Y., Voytsekhovskaya, I., Tokovenko, B., Shatilina, Z., Luzhetskyy, A., Timofeyev, M. (2017) The diversity and antibiotic properties of actinobacteria associated with endemic deepwater amphipods of Lake Baikal. Antonie Van Leeuwenhoek. 110 (12): 1593-1611.
  • Koshla, O., Lopatniuk, M., Rokytskyy, I., Yushchuk, O., Dacyuk, Y., Fedorenko, V., Luzhetskyy,A., Ostash, B. (2017) Properties of Streptomyces albus J1074 mutant deficient in tRNALeuUAA gene bldA, Arch Microbiol., 199(8):1175-1183.
  • Axenov-Gribanov, D., Tokovenko, B., Rebets, Y., Voytsekhovskaya, I., Shatilina, Z., Protasov, E., Luzhetskyy, A., Timofeyev, M. (2017) Draft Genome Sequence of Streptomyces sp. Strain IB2014011-1, Isolated from Trichoptera sp. Larvae of Lake Baikal. Genome Announc., 5 (17): e00062-17.
  • Sun, Y.Q., Busche, T., Rückert, C., Paulus, C, Rebets, Y., Novakova, R., Kalinowski, J, Luzhetskyy, A., Kormanec, J., Sekurova, O.N., Zotchev, S.B. (2017) Development of a Biosensor Concept to Detect the Production of Cluster-Specific Secondary Metabolites, ACS Synth Biol., 6 (6): 1026-1033.
  • Axenov-Gribanov, D., Voytsekhovskaya, I., Rebets, Y., Tokovenko, B., Penzina, T., Gornostay, T., Adelshin, R., Protasov, E., Luzhetskyy, A., Timofeyev, M. (2016) Actinobacteria possessing antimicrobial and antioxidant activities isolated from the pollen of scots pine (Pinus sylvestris) grown on the Baikal shore. Antonie Van Leeuwenhoek. 109 (10): 1307-22.
  • Horbal, L., Ostash, B., Luzhetskyy, A., Walker, S., Kalinowski, J., Fedorenko, V.. (2016) A gene cluster for the biosynthesis of moenomycin family antibiotics in the genome of teicoplanin producer Actinoplanes teichomyceticus. Appl Microbiol Biotechnol. 100 (17): 7629-38.
  • Yushchuk, O., Ostash, B., Pham, T.H., Luzhetskyy, A., Fedorenko, V., Truman, A.W., Horbal, L.. (2016) Characterization of the Post-Assembly Line Tailoring Processes in Teicoplanin Biosynthesis. ACS Chem Biol. 11 (8): 2254-64.
  • Axenov-Gibanov, D., Voytsekhovskaya, I., Tokovenko, B., Protasov, E., Gamaiunov, S., Rebets, Y., Luzhetskyy, A., Timofeyev, M. (2016) Actinobacteria Isolated from an Underground Lake and Moonmilk Speleothem from the Biggest Conglomeratic Karstic Cave in Siberia as Sources of Novel Biologically Active Compounds. PLoS One. 11 (3): e0152957.
  • Medema, M.H., Kottmann, R., Yilmaz, P., Cummings, M., Biggins, J.B., Blin, K., de Bruijn, I., Chooi, Y.H., Claesen, J., Coates, R.C., Cruz-Morales, P., Duddela, S., Düsterhus, S., Edwards, D.J., Fewer, D.P., Garg, N., Geiger, C., Gomez-Escribano, J.P., Greule, A., Hadjithomas, M., Haines, A.S., Helfrich, E.J., Hillwig, M.L., Ishida, K., Jones, A.C., Jones, C.S., Jungmann, K., Kegler, C., Kim, H.U., Kötter, P., Krug, D., Masschelein, J., Melnik, A.V., Mantovani, S.M., Monroe, E.A., Moore, M., Moss, N., Nützmann, H.W., Pan, G., Pati, A., Petras, D., Reen, F.J., Rosconi, F., Rui, Z., Tian, Z., Tobias, N.J., Tsunematsu, Y., Wiemann, P., Wyckoff, E., Yan, X., Yim, G., Yu, F., Xie, Y., Aigle, B., Apel, A.K., Balibar, C.J., Balskus, E.P., Barona-Gómez, F., Bechthold, A., Bode, H.B., Borriss, R., Brady, S.F., Brakhage, A.A., Caffrey, P., Cheng, Y.Q., Clardy, J., Cox, R.J., De Mot, R., Donadio, S., Donia, M.S., van der Donk, W.A., Dorrestein, P.C., Doyle, S., Driessen, A.J., Ehling-Schulz, M., Entian, K.D., Fischbach, M.A., Gerwick, L., Gerwick, W.H., Gross, H., Gust, B., Hertweck, C., Höfte, M., Jensen, S.E., Ju, J., Katz, L., Kaysser, L., Klassen, J.L., Keller, N.P., Kormanec, J., Kuipers, O.P., Kuzuyama, T., Kyrpides, N.C., Kwon, H.J., Lautru, S., Lavigne, R., Lee, C.Y., Linquan, B., Liu, X., Liu, W., Luzhetskyy, A., Mahmud, T., Mast, Y., Méndez, C., Metsä-Ketelä, M., Micklefield, J., Mitchell, D.A., Moore, B.S., Moreira, L.M., Müller, R., Neilan, B.A., Nett, M., Nielsen, J., O'Gara, F., Oikawa, H., Osbourn, A., Osburne, M.S., Ostash, B., Payne, S.M., Pernodet, J.L., Petricek, M., Piel, J., Ploux, O., Raaijmakers, J.M., Salas, J.A., Schmitt, E.K., Scott, B., Seipke, R.F., Shen, B., Sherman, D.H., Sivonen, K., Smanski, M.J., Sosio, M., Stegmann, E., Süssmuth, R.D., Tahlan, K., Thomas, C.M., Tang, Y., Truman, A.W., Viaud, M., Walton, J.D., Walsh, C.T., Weber, T., van Wezel, G.P., Wilkinson, B., Willey, J.M., Wohlleben, W., Wright, G.D., Ziemert, N., Zhang, C., Zotchev, S.B., Breitling, R., Takano, E., Glöckner, F.O. (2015) Minimum Information about a Biosynthetic Gene cluster. Nat Chem Biol. 11 (9): 625-31.
  • Wardecki, T., Brötz, E., De Ford, C., von Loewenich, F.D., Rebets, Y., Tokovenko, B., Luzhetskyy, A., Merfort, I. (2015) Endophytic Streptomyces in the traditional medicinal plant Arnica montana L.: secondary metabolites and biological activity. Antonie Van Leeuwenhoek. 108 (2): 391-402.
  • Ostash, B., Yushchuk, O., Tistechok, S., Mutenko, H., Horbal, L., Muryn, A., Dacyuk, Y., Kalinowski, J., Luzhetskyy, A., Fedorenko, V. (2015) The adpA-like regulatory gene from Actinoplanes teichomyceticus: in silico analysis and heterologous expression. World J Microbiol Biotechnol. 31 (8): 1297-301.
  • Lopatniuk, M., Ostash, B., Makitrynskyy, R., Walker, S., Luzhetskyy, A., Fedorenko, V. (2015) Testing the utility of site-specific recombinases for manipulations of genome of moenomycin producer Streptomyces ghanaensis ATCC14672. J Appl Genet. 56 (4): 547-50.
  • Wardecki, T., Brötz, E., De Ford, C., von Loewenich, F.D., Rebets, Y., Tokovenko, B., Luzhetskyy, A., Merfort, I. (2015) Endophytic Streptomyces in the traditional medicinal plant Arnica montana L.: secondary metabolites and biological activity. Antonie Van Leeuwenhoek. 108 (2): 391-402.
  • Horbal, L., Kobylyanskyy, A., Truman, A.W., Zaburranyi, N., Ostash, B., Luzhetskyy, A.,Marinelli, F., Fedorenko, V. (2014) The pathway‐specific regulatory genes, tei15* and tei16*, are the master switches of teicoplanin production in Actinoplanes teichomyceticus. Appl Microbiol Biotechnol. 98 (22): 9295‐309.
  • Lopatniuk, M., Ostash, B., Luzhetskyy, A., Walker, S., Fedorenko, V. (2014) Generation and study of the strains of streptomycetes ‐ heterologous hosts for production of moenomycin. Russ J Genet. 50 (4): 360‐365.
  • Raju, R., Gromyko, O., Andriy, B., Fedorenko, V., Luzhetskyy, A., Müller, R. (2014) Oleamycins A and B: new antibacterial cyclic hexadepsipeptides isolated from a terrestrial Streptomyces sp. J Antibiot (Tokyo) in print.
  • Ostash, B., Campbell, J., Luzhetskyy, A. and Walker, S. (2013) MoeH5: a natural glycorandomizer from the moenomycin biosynthetic pathway. Mol Microbiol. 90 (6):1324‐1338.
  • Horbal, L., Kobylyanskyy, A., Yushchuk, O., Zaburannyi, N., Luzhetskyy, A., Ostash, B., Marinelli, F. and Fedorenko, V. (2013) Evaluation of heterologous promoters for genetic analysis of Actinoplanes teichomyceticus‐Producer of teicoplanin, drug of last defense. J Biotechnol. 168 (4):367‐372.
  • Raju, R., Gromyko, O., Fedorenke,V., Luzhetskyy,A. and Müller, R. (2013) Lorneic acids C and D, new trialkyl‐substituted aromatic acids isolated from a terrestrial Streptomyces sp. The Journal of Antibiotics (Tokyo), 66 (6): 347‐349.
  • Makitrynskyy, R., Ostash, B., Tsypik, O., Rebets, Y., Doud, E., Meredith, T., Luzhetskyy, A., Bechthold, A., Walker, S. and Fedorenko, V. (2013) Pleiotropic regulatory genes bldA, adpA and absB are implicated in production of phosphoglycolipid antibiotic moenomycin. Open Biol. 3 (10): 130121.
  • Raju, R., Gromyko, O., Fedorenko, V., Herrmann, J., Luzhetskyy, A. and Müller, R. (2013)Rubimycinone A, a new anthraquinone from a terrestrial Streptomyces sp. Tetrahedron Letters, 54 (8): 900‐902.
  • Raju R., Gromyko O., Fedorenko V., Luzhetskyy, A. and Müller R. (2013) Oleaceran: A Novel Spiro [isobenzofuran‐1,2'‐naptho[1,8‐bc]furan] Isolated from a Terrestrial Streptomyces sp. Organic Letters, 15 (14): 3487‐3489.
  • Strobel, T., Schmidt, Y., Linnenbrink, A., Luzhetskyy, A., Luzhetska, M., Taguchi, T., Brötz, E., Paululat, T., Stasevych, M., Stanko, O., Novikov, V. and Bechthold, A. (2013) Tracking down biotransformation to the genetic level: Identfication of a highly flexible glycosyltransferase from Saccharothrix espanaensis. Appl. and Environm. Microbiology, 79 (17): 5224‐5232.
  • Raju, R., Gromyko, O., Fedorenko, V., Luzhetskyy, A., Plaza, A. and Müller, R. (2012) Juniperolide A: A new polyketide isolated from a terrestrial actinomycete, Streptomyces sp. Organic Letters, 14 (23): 5860‐5863.
  • Raju, R., Gromyko, O., Fedorenko, V., Luzhetskyy, A. and Müller, R. (2012) Leopolic acid A, isolated from a terrestrial actinomycete, Streptomyces sp., Tetrahedron Letters 53 (14): 6300‐6301.
  • Raju, R, Gromyko, O., Fedorenko, O., Luzhetskyy, A. and Müller, R. (2012) Pimprinols A–C, from the terrestrial actinomycete, Streptomyces sp. Tetrahedron Letters, 53 (24): 3009‐3011.
  • Horbal, L., Rebets, Y., Rabyk, M., Makitrynskyy, R., Luzhetskyy, A., Fedorenko, V. and Bechthold, A. (2012) SimReg1 is a master switch for biosynthesis and export of simocyclinone D8 and its precursors. AMB Express, 2 (1):1‐8.
  • Härle, J., Günther, S., Lauinger, B., Weber, M., Kammerer, B., Zechel, D.L., Luzhetskyy, A. and Bechthold, A. (2011) Rational design of an aryl‐C‐glycoside catalyst from a natural product O‐glycosyltransferase. ChemBiol, 18 (4): 520‐530.
  • Ostash, B., Ostash, I., Zhu, L., Kharel, M.K., Luzhetskyy, A., Bechthold ,A., Walker, S., Rohr, J., and Fedorenko, V. (2010) Properties of lanK‐based regulatory circuit involved in landomycin biosynthesis in Streptomyces cyanogenus S136. Genetika, 46 (5): 604‐609.
  • Horbal, L., Rebets, Y., Rabyk, M., Luzhetskyy, A., Ostash, B., Welle, E., Nakamura, T., Fedorenko, V. and Bechthold, A. (2010) Characterization and analysis of the regulatory network involved in control of lipomycin biosynthesis in Streptomyces aureofaciens Tü117. Appl. Microbiol. Biotechnol., 85 (4): 1069‐1079.
  • Erb, A., Luzhetskyy, A., Hardter, U. and Bechthold, A. (2009) Cloning and sequencing of the biosynthetic gene cluster for saquayamycin Z and galtamycin B and elucidating the assembly of their saccharide chains. ChemBioChem, 10 (8): 1392‐1401
  • Krauth, C., Fedoryshyn, M., Schleberger, C., Luzhetskyy, A. and Bechthold, A. (2009) Engineering a function into a glycosyltransferase. ChemBiol, 16 (1): 28‐35.
  • Erb, A., Krauth, C., Luzhetskyy, A. and Bechthold, A. (2009) Differences in the substrate specificity of glycosyltransferases involved in landomycins A and E biosynthesis. Appl. Microbiol. Biotechnol., 83 (6): 1067‐1076.
  • Ostash, I., Ostash, B., Luzhetskyy, A., Bechthold, A., Walker, S. and Fedorenko, V. (2008) Coordination of export and glycosylation of landomycins in Streptomyces cyanogenus S136. FEMS Microbiol. Lett., 285 (2): 195‐202.
  • Rebets, Y., Dutko, L., Ostash, B., Luzhetskyy, A., Kulachkovskyy, O., Yamaguchi, T., Nakamura, T., Bechthold, A. and Fedorenko, V. (2008) Function of lanI in regulation of landomycin A biosynthesis in Streptomyces cyanogenus S136 and cross‐complementation studies with Streptomyces antibiotic regulatory proteins encoding genes. Arch Microbiol.,189 (2): 111‐120.
  • Fedoryshyn, M., Nur‐e‐Alam, M., Zhu, L., Luzhetskyy, A., Rohr, J. and Bechthold, A. (2007) Surprising production of a new urdamycin derivative by S. fradiae urdQ/R. J Biotechnol., 130 (1): 32‐38.
  • Zhu, L., Luzhetskyy, A., Luzhetska, M., Mattingly, C., Adams, V., Bechthold, A. and Rohr, J. (2007) Generation of New Landomycins with Altered Saccharide Patterns through Overexpression
    of the Glycosyltransferase Gene lanGT3 in the Biosynthetic Gene Cluster of Landomycin A in Streptomyces cyanogenus S‐136. ChemBioChem, 8 (1): 83‐88.
  • Dürr, C., Schnell, H.J., Luzhetskyy, A., Murillo, R., Weber, M., Welzel, K., Vente, A. and Bechthold, A. (2006) Biosynthesis of the terpene phenalinolactone in Streptomyces sp. Tü6071: analysis of the gene cluster and generation of derivatives. ChemBiol., 13 (4): 365‐377.
  • Sianidis, G., Wohlert, S.E., Pozidis, C., Karamanou, S., Luzhetskyy, A., Vente, A. and Economou, A. (2006) Cloning, purification and characterization of a functional anthracycline glycosyltransferase. J Biotechnol., 125 (3): 425‐433.
  • Baig, I., Kharel, M., Kobylyanskyy, A., Zhu, L., Rebets, Y., Ostash, B., Luzhetskyy, A., Bechthold, A., Fedorenko, V. and Rohr, J. (2006) On the Acceptor Substrate of CGlycosyltransferase UrdGT2: Three Prejadomycin C‐Glycosides from an Engineered Mutant of Streptomyces globisporus 1912 lndE(urdGT2). Angewandte Chemie Int. Ed., 45 (46): 7842‐7846.
  • Dutko, L., Rebets, Y., Ostash, B., Luzhetskyy, A., Bechthold, A., Nakamura, T. and Fedorenko, V. (2006) A putative proteinase gene is involved in regulation of landomycin E biosynthesis in Streptomyces globisporus1912. FEMS Microbiol Lett., 255 (2): 280‐285.
  • Ostash, B.E., Ogonyan, S.V., Luzhetskyy, A., Bechthold, A. and Fedorenko, V.A. (2005) The use of PCR for detecting genes that encode type I polyketide synthases in genomes of Actinomycetes. Russian Journal of Genetics / Genetika, 41 (5): 473‐478 / 2005: 41(5): 595‐
    600.
  • Mayer, A., Taguchi, T., Linnenbrink, A., Hofmann, C., Luzhetskyy, A. and Bechthold, A. (2005) LanV, a bifunctional enzyme: aromatase and ketoreductase during landomycin A biosynthesis, Chembiochem, 6 (12): 2312‐2315.
  • Rebets, Y, Ostash, B, Luzhetskyy, A., Kushnir, S, Fukuhara, M, Bechthold, A, Nashimoto, M, Nakamura, T and Fedorenko, V. (2005) DNA‐binding activity of LndI protein and temporal expression of the gene that upregulates landomycin E production in Streptomyces globisporus 1912. Microbiology, 151 (1): 281‐290.
  • Zhu, L., Ostash, B., Rix, U., Nur‐E‐Alam, M., Mayer, A., Luzhetskyy, A., Mendez, C., Salas, J.A., Bechthold, A., Fedorenko, V. and Rohr, J. (2005) Identification of the function of gene lndM2 encoding a bifunctional oxygenase‐reductase involved in the biosynthesis of the antitumor antibiotic landomycin E by Streptomyces globisporus 1912 supports the
    originally assigned structure for Landomycinone. Journal of Organic Chemistry, 70 (2): 631‐638.
  • Gromyko, O., Rebets, Y., Ostash, B., Luzhetskyy, A., Fukuhara, M., Bechthold, A., Nakamura, T. and Fedorenko, V. (2004) Generation of Streptomyces globisporus SMY622 strain with increased landomycin E production and it's initial characterization. J Antibiotics, 57 (6): 383‐389.
  • Ostash, B., Rix, U., Rix, L., Liu, T., Lombo, F., Luzhetskyy, A., Gromyko, O., Wang, C., Brana, A., Mendez, C., Salas, J.A., Fedorenko, V. and Rohr, J. (2004) Generation of new landomycins by combinatorial biosynthetic manipulation of the LndGT4 gene of the landomycin E cluster in S. globisporus. Chem Biol., 11 (4): 547‐555.
  • Mulert, U., Luzhetskyy, A., Hofmann, C., Mayer, A. and Bechthold, A. (2004) Expression of the landomycin biosynthetic gene cluster in a PKS mutant of Streptomyces fradiae is dependent on the coexpression of a putative transcriptional activator geneFEMS Microbiol Lett., 230 (1):91‐97.
  • Rebets, Y., Ostash, B., Luzhetskyy, A., Hoffmeister, D., Brana, A., Mendez, C., Salas, J., Bechthold, A. and Fedorenko, V. (2003) Production of landomycins in Streptomyces globisporus 1912 and S cyanogenus S136 is regulated by genes encoding putative transcriptional activators. FEMS Microbiol Lett., 222 (1): 149‐153.

Patents

  • Patent application PF 76081 SE/CRU "Gene Cluster for biosynthesis of Pamamycin".
  • European patent application Nr.07.017025.3 “ Herstellung von genetisch modifizierten Aktinomyceten durch Rekombination”.
  • Ukrainian national patent Nr:62200A „Obtaining method of Streptomyces globisporus 1912 landomycin E overproducers”.
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