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Study of the Effect of Lower Eukaryotes on Tacrolimus (FK-506) Biosynthesis by the Streptomyces tsukubensis Strain VKM Ac-2618D

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Abstract

The effect of inactivated yeast cells, individual components of the yeast cells, and the inactivated biomass of filamentous fungi (micromycetes) of various taxonomic positions on the biosynthesis of immunosuppressant tacrolimus (FK-506) by Streptomyces tsukubensis VKM Ac-2618D cells has been studied. The fractions of soluble and insoluble components of yeast cells positively influenced tacrolimus biosynthesis; the FK-506 concentrations reached 447.1± 22.4 mg/L and 514.3 ± 25.7 mg/L, respectively. The insoluble cell components, including the cell walls and cytoplasmic membranes, had a greater effect than other fractions. The presence of whole baker’s yeast cells and the filamentous fungus Aspergillus ochraceus biomass in the complex nutrient medium stimulated tacrolimus production by S. tsukubensis VKM Ac-2618D (667.5 ± 33.4 mg/L and 633.5 ± 31.7 mg/L, respectively). The biomass of deuteromycete Curvularia lunata had no effect on FK‑506 biosynthesis (288.4 ± 14.4 mg/L). Conversely, the biomass of the Gongronella butleri fungus fully inhibited growth and tacrolimus production in S. tsukubensis. The increase in FK-506 biosynthesis in the presence of the cells of the tested micromycetes is more likely due to the polysaccharide composition of their cell walls than to the ergosterol content. The results expand the knowledge of S. tsukubensis physiology and may be useful for the development of the biotechnological process of tacrolimus production.

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Funding

The study was supported by the Foundation for Assistance to Small Innovative Enterprises (FASIE) program UMNIK 16-12 (project no. 12081GU/2017).

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Authors and Affiliations

  1. Pushchino State Natural Science Institute, 142290, Pushchino, Moscow oblast, Russia

    V. Yu. Poshekhontseva

  2. Pushchino Scientific Center for Biological Research of the Russian Academy of Sciences, G.K. Skryabin Institute of Biochemistry and Physiology of Microorganisms, 142290, Pushchino, Moscow oblast, Russia

    V. Yu. Poshekhontseva, V. V. Fokina, G. V. Sukhodolskaya, A. A. Shutov & M. V. Donova

  3. Pharmins, Ltd., 142290, Pushchino, Moscow oblast, Russia

    V. V. Fokina & M. V. Donova

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  1. V. Yu. Poshekhontseva
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Correspondence to V. V. Fokina.

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Translated by I. Gordon

Abbreviations: CL—culture liquid; DYP—dry baker’s yeast powder; FK-506—tacrolimus; HPLC—high-performance liquid chromatography; FKBP12—FK-506-binding protein.

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Poshekhontseva, V.Y., Fokina, V.V., Sukhodolskaya, G.V. et al. Study of the Effect of Lower Eukaryotes on Tacrolimus (FK-506) Biosynthesis by the Streptomyces tsukubensis Strain VKM Ac-2618D. Appl Biochem Microbiol 56, 847–853 (2020). https://doi.org/10.1134/S0003683820080062

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