The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020crobial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

The Silent Crisis

The Silent Crisis

“Fungal infections are an overlooked emerging disaster” Kainz et al., Microbial Cell, June 2020

Publications

The extensive research behind BSG005

Biosergen’s antifungal drug candidate BSG005 is based on two decades of scientific work at Norge’s Teknisk-Videnskabelige Universitet (NTNU) in Trondheim in collaboration with the Department of Biotechnology and Nanomedicine at SINTEF, originally funded by the Research Council of Norway.

Peer reviewed scientific publications from SINTEF, NTNU and the Company describing various aspects of the work to get to BSG005 Located in Trondheim, Norway, SINTEF is one of Europe’s largest private research institutions with more than 2,000 employees.

  1. Sekurova O, Sletta H, Ellingsen TE, Valla S, Zotchev S: Molecular cloning and analysis of a pleiotropic regulatory gene locus from the nystatin producer Streptomyces noursei ATCC11455. Fems Microbiology Letters 1999, 177(2):297-304.
  2. Brautaset T, Sekurova ON, Sletta H, Ellingsen TE, Strom AR, Valla S, Zotchev SB: Biosynthesis of the polyene antifungal antibiotic nystatin in Streptomyces noursei ATCC 11455: analysis of the gene cluster and deduction of the biosynthetic pathway. Chemistry & Biology 2000, 7(6):395-403.
  3. Zotchev S, Haugan K, Sekurova O, Sletta H, Ellingsen TE, Valla S: Identification of a gene cluster for antibacterial polyketide-derived antibiotic biosynthesis in the nystatin producer Streptomyces noursei ATCC 11455. Microbiology-Uk 2000, 146:611-619.
  4. Brautaset T, Bruheim P, Sletta H, Hagen L, Ellingsen TE, Strom AR, Valla S, Zotchev SB: Hexaene derivatives of nystatin produced as a result of an induced rearrangement within the nysC polyketide synthase gene in S. noursei ATCC 11455. Chemistry & Biology 2002, 9(3):367-373.
  5. Aparicio JF, Caffrey P, Gil JA, Zotchev SB: Polyene antibiotic biosynthesis gene clusters. Applied Microbiology and Biotechnology 2003, 61(3):179-188.
  6. Brautaset T, Borgos SEF, Sletta H, Ellingsen TE, Zotchev SB: Site-specific mutagenesis and domain substitutions in the loading module of the nystatin polyketide synthase, and their effects on nystatin biosynthesis in Streptomyces noursei. Journal of Biological Chemistry 2003, 278(17):14913-14919.
  7. Bruheim P, Borgos SEF, Tsan P, Sletta H, Ellingsen TE, Lancelin JM, Zotchev SB: Chemical diversity of polyene macrolides produced by Streptomyces noursei ATCC 11455 and recombinant strain ERD44 with genetically altered polyketide synthase NysC. Antimicrobial Agents and Chemotherapy 2004, 48(11):4120-4129.
  8. Sekurova ON, Brautaset T, Sletta H, Borgos SEF, Jakobsen OM, Ellingsen TE, Strom AR, Valla S, Zotchev SB: In vivo analysis of the regulatory genes in the nystatin biosynthetic gene cluster of Streptomyces noursei ATCC 11455 reveals their differential control over antibiotic biosynthesis. Journal of Bacteriology 2004, 186(5):1345-1354.
  9. Fjaervik E, Zotchev SB: Biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei. Applied Microbiology and Biotechnology 2005, 67(4):436-443.
  10. Sletta H, Borgos SEF, Bruheim P, Sekurova ON, Grasdalen H, Aune R, Ellingsen TE, Zotchev SB: Nystatin biosynthesis and transport: nysH and nysG genes encoding a putative ABC transporter system in Streptomyces noursei ATCC 11455 are required for efficient conversion of 10-deoxynystatin to nystatin. Antimicrobial Agents and Chemotherapy 2005, 49(11):4576-4583.
  11. Volokhan O, Sletta H, Sekurova ON, Ellingsen TE, Zotchev SB: An unexpected role for the putative 4 '-phosphopantetheinyl transferase-encoding gene nysF in the regulation of nystatin blosynthesis in Streptomyces noursei ATCC 11455. Fems Microbiology Letters 2005, 249(1):57-64.
  12. Borgos SEF, Sletta H, Fjaervik E, Brautaset T, Ellingsen TE, Gulliksen OM, Zotchev SB: Effect of glucose limitation and specific mutations in the module 5 enoyl reductase domains in the nystatin and amphotericin polyketide synthases on polyene macrolide biosynthesis. Archives of Microbiology 2006, 185(3):165-171.
  13. Borgos SEF, Tsan P, Sletta H, Ellingsen TE, Lancelin JM, Zotchev SB: Probing the structure-function relationship of polyene macrolides: Engineered biosynthesis of soluble nystatin analogues. Journal of Medicinal Chemistry 2006, 49(8):2431-2439.
  14. Volokhan O, Sletta H, Sekurova ON, Ellingsen TE, Zotchev SB: An unexpected role for the putative 4 '-phosphopantetheinyl transferase-encoding gene nysF in the regulation of nystatin blosynthesis in Streptomyces noursei ATCC 11455. Fems Microbiology Letters 2005, 249(1):57-64.
  15. Borgos SEF, Sletta H, Fjaervik E, Brautaset T, Ellingsen TE, Gulliksen OM, Zotchev SB: Effect of glucose limitation and specific mutations in the module 5 enoyl reductase domains in the nystatin and amphotericin polyketide synthases on polyene macrolide biosynthesis. Archives of Microbiology 2006, 185(3):165-171.
  16. Borgos SEF, Tsan P, Sletta H, Ellingsen TE, Lancelin JM, Zotchev SB: Probing the structure-function relationship of polyene macrolides: Engineered biosynthesis of soluble nystatin analogues. Journal of Medicinal Chemistry 2006, 49(8):2431-2439.
  17. Volokhan O, Sletta H, Ellingsen TE, Zotchev SB: Characterization of the P450 monooxygenase NysL, responsible for C-10 hydroxylation during biosynthesis of the polyene macrolide antibiotic nystatin in Streptomyces noursei. Applied and Environmental Microbiology 2006, 72(4):2514-2519.
  18. Nedal A, Sletta H, Brautaset T, Borgos SEF, Sekurova ON, Ellingsen TE, Zotchev SB: Analysis of the mycosamine biosynthesis and attachment genes in the nystatin Biosynthetic gene cluster of Streptomyces noursei ATCC 11455. Applied and Environmental Microbiology 2007, 73(22):7400-7407.
  19. Brautaset T, Sletta H, Nedal A, Borgos SEF, Degnes KF, Bakke I, Volokhan O, Sekurova ON, Treshalin ID, Mirchink EP et al: Improved Antifungal Polyene Macrolides via Engineering of the Nystatin Biosynthetic Genes in Streptomyces noursei. Chemistry & Biology 2008, 15(11):1198-1206.
  20. Caffrey P, Aparicio JF, Malpartida F, Zotchev SB: Biosynthetic engineering of polyene macrolides towards generation of improved antifungal and antiparasitic agents. Current Topics in Medicinal Chemistry 2008, 8(8):639-653.
  21. Preobrazhenskaya MN, Olsufyeva EN, Solovieva SE, Tevyashova AN, Reznikova MI, Luzikov YN, Terekhova LP, Trenin AS, Galatenko OA, Treshalin ID et al: Chemical Modification and Biological Evaluation of New Semisynthetic Derivatives of 28,29-Didehydronystatin A(1) (S44HP), a Genetically Engineered Antifungal Polyene Macrolide Antibiotic. Journal of Medicinal Chemistry 2009, 52(1):189-196.
  22. Zotchev S, Caffrey P: GENETIC ANALYSIS OF NYSTATIN AND AMPHOTERICIN BIOSYNTHESIS. In: Complex Enzymes in Microbial Natural Product Biosynthesis, Part B: Polyketides, Aminocoumarins and Carbohydrates. Edited by Hopwood DA, vol. 459; 2009: 243-258.
  23. Preobrazhenskaya MN, Olsufyeva EN, Tevyashova AN, Printsevskaya SS, Solovieva SE, Reznikova MI, Trenin AS, Galatenko OA, Treshalin ID, Pereverzeva ER et al: Synthesis and study of the antifungal activity of new mono- and disubstituted derivatives of a genetically engineered polyene antibiotic 28,29-didehydronystatin A(1) (S44HP). Journal of Antibiotics 2010, 63(2):55-64.
  24. Brautaset T, Sletta H, Degnes KF, Sekurova ON, Bakke I, Volokhan O, Andreassen T, Ellingsen TE, Zotchev SB: New Nystatin-Related Antifungal Polyene Macrolides with Altered Polyol Region Generated via Biosynthetic Engineering of Streptomyces noursei. Applied and Environmental Microbiology 2011, 77(18):6636-6643.
  25. Heia S, Borgos SEF, Sletta H, Escudero L, Seco EM, Malpartida F, Ellingsen TE, Zotchev SB: Initiation of Polyene Macrolide Biosynthesis: Interplay between Polyketide Synthase Domains and Modules as Revealed via Domain Swapping, Mutagenesis, and Heterologous Complementation. Applied and Environmental Microbiology 2011, 77(19):6982-6990.
  26. Tevyashova AN, Olsufyeva EN, Solovieva SE, Printsevskaya SS, Reznikova MI, Trenin AS, Galatenko OA, Treshalin ID, Pereverzeva ER, Mirchink EP et al: Structure-Antifungal Activity Relationships of Polyene Antibiotics of the Amphotericin B Group. Antimicrobial Agents and Chemotherapy 2013, 57(8):3815-3822.