Abstract
The dependence of biosynthesis of macrolide immunosuppressive agent tacrolimus (FK-506) in starch-containing media by the Streptomyces tsukubaensis VKM Ac-2618D strain on the molecular weight and composition of potato starch polysaccharides was studied. It was shown that the use of high-molecular branched starches as a carbon source provided a higher tacrolimus yield as compared to linear low-molecular polysaccharides at the similar culture growth indicators. The approaches providing the highest rate of tacrolimus biosynthesis by using high- and low-molecular starches and dextrins have been proposed. The biosynthesis process carrying out under the periodic batch cultivation with fractional starch feeding increased the tacrolimus yield significantly (up to 2 times), maintained biomass at a high level and reduced destructive processes rates. The maximum tacrolimus titer was observed when high-molecular potato starches were added to the culture in the retardation growth phase, while the best positive effect for low-molecular starches and dextrins additives was noted at stationary growth phase. The results could be useful in creating biotechnology for the production of pharmaceutical tacrolimus.
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Funding
This work was carried out within the State Assignment (Fokina V.V., Shutov A.A., Donova M.V.). Poshekhontseva V.Yu. is grateful to the FASIE (program UMNIK 16–12, Grant no. 12081GU/2017) for supporting her work.
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Poshekhontseva, V.Y., Fokina, V.V., Sukhodolskaya, G.V. et al. Effect of Starch Composition on the Biosynthesis of Immunosuppressant Tacrolimus (FK-506) by Streptomyces tsukubaensis VKM Ac-2618D Strain. Appl Biochem Microbiol 55, 534–543 (2019). https://doi.org/10.1134/S0003683819040148
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DOI: https://doi.org/10.1134/S0003683819040148