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Biosynthesis of Tacrolimus by the Streptomyces tsukubensis VKM Ac-2618D Strain in the Presence of Polymeric Sorbents and Development of a Method for Its Isolation and Purification

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Abstract

Tacrolimus is known as the most effective immunosuppressive drug which is synthesized by actinobacteria of the genus Streptomyces. Its biosynthesis is accompanied by the formation of the structural analogs. A new method for the production of tacrolimus by Streptomyces tsukubensis BKM Ac-2618D with the use of brominated styrene-divinylbenzene sorbent SP-207 was developed. This approach enabled to increase the yield, prevent undesirable destruction, and simplify the tacrolimus isolation procedure from the cultivation media. The preliminary separation step was optimized by means of the usage of regenerable sorbents such as methylmethacrylate (HP2MG) and chemically modified silica gel (Diasorb-100-Diol). By implementation of the silica gel-based cation exchange resins pretreated with silver ions for the final purification stage, it was possible to increase its productivity. The overall yield of tacrolimus by this method was found to around 60–70%. The results could be implemented for the full-cycle production development of the pharmaceutical grade tacrolimus.

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Funding

This work was financially supported by the state assignment (project no. AAAA-A16-116062110077-6).

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Authors and Affiliations

  1. Chemistry Department of the Lomonosov Moscow State University, 119234, Moscow, Russia

    D. S. Salionov & S. M. Staroverov

  2. “BioChemMack S&T”, 119234, Moscow, Russia

    D. S. Salionov, G. G. Vasiarov, E. V. Titova, V. S. Karasev & S. M. Staroverov

  3. PSCBR RAS, Skryabin Institute of Biochemistry and Physiology of Microorganisms, Russian Academy of Sciences, 142290, Pushchino, Moscow oblast, Russia

    V. Yu. Poshekhontseva, V. V. Fokina, A. A. Shutov, V. M. Nikolaeva & M. V. Donova

  4. “Pharmins”, 142290, Pushchino, Moscow oblast, Russia

    V. Yu. Poshekhontseva, V. V. Fokina, A. A. Shutov, V. M. Nikolaeva & M. V. Donova

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  1. D. S. Salionov
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  2. V. Yu. Poshekhontseva
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  3. V. V. Fokina
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  4. A. A. Shutov
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  5. V. M. Nikolaeva
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  6. G. G. Vasiarov
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  7. E. V. Titova
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  8. V. S. Karasev
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  9. S. M. Staroverov
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  10. M. V. Donova
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Correspondence to V. V. Fokina.

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The authors declare that they have no conflict of interest. This article does not contain any studies involving animals or human participants performed by any of the authors.

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Salionov, D.S., Poshekhontseva, V.Y., Fokina, V.V. et al. Biosynthesis of Tacrolimus by the Streptomyces tsukubensis VKM Ac-2618D Strain in the Presence of Polymeric Sorbents and Development of a Method for Its Isolation and Purification. Appl Biochem Microbiol 56, 699–707 (2020). https://doi.org/10.1134/S0003683820060150

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  • DOI: https://doi.org/10.1134/S0003683820060150

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